Succinoylamino lactams as inhibitors of A-beta protein production

ABSTRACT

This invention relates to novel lactams having drug and bio-affecting properties, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein and, more specifically, inhibit the production of Aβ-peptide, thereby acting to prevent the formation of neurological deposits of amyloid protein. More particularly, the present invention relates to the treatment of neurological disorders related to β-amyloid production such as Alzheimer&#39;s disease and Down&#39;s Syndrome.

RELATED CROSS-REFERENCES

This application is a continuation of U.S. patent application Ser. No.11/175,644, filed Jul. 6, 2005, which is a divisional of U.S. patentapplication Ser. No. 10/285,776, filed Nov. 1, 2002, which is adivisional of U.S. patent application Ser. No. 09/506,360, filed Feb.17, 2000, now U.S. Pat. No. 6,794,381, issued Sep. 21, 2004, which is acontinuation-in-part of U.S. patent application Ser. No. 09/370,089,filed Aug. 6, 1999, now abandoned, Provisional Application Ser. No.60/095,698, filed Aug. 7, 1998 (expired), and Provisional U.S. PatentApplication Ser. No. 60/120,227, filed Feb. 15, 1999 (expired), andProvisional Application Ser. No. 60/113,558, filed Dec. 23, 1998(expired); the disclosures of which are hereby incorporated by referencein their entirety.

FIELD OF THE INVENTION

This invention relates to novel lactams having drug and bio-affectingproperties, their pharmaceutical compositions and methods of use. Thesenovel compounds inhibit the processing of amyloid precursor protein and,more specifically, inhibit the production of Aβ-peptide, thereby actingto prevent the formation of neurological deposits of amyloid protein.More particularly, the present invention relates to the treatment ofneurological disorders related to β-amyloid production such asAlzheimer's disease and Down's Syndrome.

BACKGROUND OF THE INVENTION

Alzheimer's disease (AD) is a degenerative brain disorder characterizedclinically by progressive loss of memory, temporal and localorientation, cognition, reasoning, judgment and emotional stability. ADis a common cause of progressive dementia in humans and is one of themajor causes of death in the United States. AD has been observed in allraces and ethnic groups worldwide, and is a major present and futurehealth problem. No treatment that effectively prevents AD or reversesthe clinical symptoms and underlying pathophysiology is currentlyavailable (for review, Dennis J. Selkoe; Cell Biology of the amyloid(beta)-protein precursor and the mechanism of Alzheimer's disease, AnnuRev Cell Biol, 1994, 10: 373-403).

Histopathological examination of brain tissue derived upon autopsy orfrom neurosurgical specimens in effected individuals revealed theoccurrence of amyloid plaques and neurofibrillar tangles in the cerebralcortex of such patients. Similar alterations were observed in patientswith Trisomy 21 (Down's Syndrome) and hereditary cerebral hemorrhagewith amyloidosis of the Dutch-type. Neurofibrillar tangles arenonmembrane-bound bundles of abnormal proteinaceous filaments andbiochemical and immunochemical studies led to the conclusion that theirprinciple protein subunit is an altered phosphorylated form of the tauprotein (reviewed in Selkoe, 1994).

Biochemical and immunological studies revealed that the dominantproteinaceous component of the amyloid plaque is an approximately 4.2kilodalton (kD) protein of about 39 to 43 amino acids. This protein wasdesignated Aβ, β-amyloid peptide, and sometimes β/A4; referred to hereinas Aβ. In addition to deposition of Aβ in amyloid plaques, Aβ is alsofound in the walls of meningeal and parenchymal arterioles, smallarteries, capillaries, and sometimes, venules. Aβ was first purified,and a partial amino acid reported, in 1984 (Glenner and Wong, Biochem.Biophys. Res. Commun. 120: 885-890). The isolation and sequence data forthe first 28 amino acids are described in U.S. Pat. No. 4,666,829.

Compelling evidence accumulated during the last decade revealed that Aβis an internal polypeptide derived from a type 1 integral membraneprotein, termed β amyloid precursor protein (APP). β APP is normallyproduced by many cells both in vivo and in cultured cells, derived fromvarious animals and humans. Aβ is derived from cleavage of β APP by asyet unknown enzyme (protease) system(s), collectively termed secretases.

The existence of at least four proteolytic activities has beenpostulated. They include β secretase(s), generating the N-terminus ofAβ, a secretase(s) cleaving around the 16/17 peptide bond in Aβ, and γsecretases, generating C-terminal Aβ fragments ending at position 38,39, 40, 42, and 43 or generating C-terminal extended precursors whichare subsequently truncated to the above polypeptides.

Several lines of evidence suggest that abnormal accumulation of Aβ playsa key role in the pathogenesis of AD. Firstly, Aβ is the major proteinfound in amyloid plaques. Secondly, Aβ is neurotoxic and may be causallyrelated to neuronal death observed in AD patients. Thirdly, missense DNAmutations at position 717 in the 770 isoform of β APP can be found ineffected members but not unaffected members of several families with agenetically determined (familiar) form of AD. In addition, several otherβ APP mutations have been described in familiar forms of AD. Fourthly,similar neuropathological changes have been observed in transgenicanimals overexpressing mutant forms of human b APP. Fifthly, individualswith Down's syndrome have an increased gene dosage of β APP and developearly-onset AD. Taken together, these observations strongly suggest thatAβ depositions may be causally related to the AD.

It is hypothesized that inhibiting the production of Aβ will prevent andreduce neurological degeneration, by controlling the formation ofamyloid plaques, reducing neurotoxicity and, generally, mediating thepathology associated with Aβ production. One method of treatment methodswould therefore be based on drugs that inhibit the formation of Aβ invivo.

Methods of treatment could target the formation of Aβ through theenzymes involved in the proteolytic processing of b amyloid precursorprotein. Compounds that inhibit b or g secretase activity, eitherdirectly or indirectly, could control the production of Aβ.Advantageously, compounds that specifically target g secretases, couldcontrol the production of Aβ. Such inhibition of β or γ secretases couldthereby reduce production of Aβ, which, thereby, could reduce or preventthe neurological disorders associated with Aβ protein.

PCT publication number WO 96/29313 discloses the general formula:

covering metalloprotease inhibiting compounds useful for the treatmentof diseases associated with excess and/or unwanted matrixmetalloprotease activity, particularly collagenase and or stromelysinactivity.

Compounds of general formula:

are disclosed in PCT publication number WO 95/22966 relating to matrixmetalloprotease inhibitors. The compounds of the invention are usefulfor the treatment of conditions associated with the destruction ofcartilage, including corneal ulceration, osteoporosis, periodontitis andcancer.

European Patent Application number EP 0652009A1 relates to the generalformula:

and discloses compounds that are protease inhibitors that inhibit Aβproduction.

U.S. Pat. No. 5,703,129 discloses the general formula:

which covers 5-amino-6-cyclohexyl-4-hydroxy-hexanamide derivatives thatinhibit Aβ production and are useful in the treatment of Alzheimer'sdisease.

None of the above references teaches or suggests the compounds of thepresent invention which are described in detail below.

SUMMARY OF THE INVENTION

One object of the present invention is to provide novel compounds whichare useful as inhibitors of the production of Aβ protein orpharmaceutically acceptable salts or prodrugs thereof.

It is another object of the present invention to provide pharmaceuticalcompositions comprising a pharmaceutically acceptable carrier and atherapeutically effective amount of at least one of the compounds of thepresent invention or a pharmaceutically acceptable salt or prodrug formthereof.

It is another object of the present invention to provide a method fortreating degenerative neurological disorders comprising administering toa host in need of such treatment a therapeutically effective amount ofat least one of the compounds of the present invention or apharmaceutically acceptable salt or prodrug form thereof.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat compounds of Formula (I):

or pharmaceutically acceptable salt or prodrug forms thereof, whereinR³, R^(3a), R⁵, R^(5a), R⁶, A, Q, B, W, X, Y, and Z are defined below,are effective inhibitors of the production of Aβ.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Thus, in a first embodiment, the present invention provides a novelcompound of Formula (I):

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   A is O or S;-   Q is —OR¹ or —NR¹R²;-   R¹, at each occurrence, is independently selected from:    -   H;    -   C₁-C₆ alkyl substituted with 0-3 R^(1a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(1a);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(1b);    -   C₆-C₁₀ aryl substituted with 0-3 R^(1b); and    -   5 to 10 membered heterocycle substituted with 0-3 R^(1b);-   R^(1a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(1b);    -   C₆-C₁₀ aryl substituted with 0-3 R^(1b); and    -   5 to 6 membered heterocycle substituted with 0-3 R^(1b);-   R^(1b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R² is independently selected from H, NH₂, OH, C₁-C₆ alkyl, C₁-C₆    alkoxy, phenoxy, benzyloxy, C₃-C₁₀ carbocycle, C₆-C₁₀ aryl and 5 to    10 membered heterocycle;-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—N(R^(7b))C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—S(═O)₂N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, 2, or 3;-   m is 0, 1, 2, or 3;-   R^(3a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₂-C₄ alkenyloxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₁-C₆ alkoxy substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;-   R⁶ is H;    -   C₁-C₆ alkyl substituted with 0-3 R^(6a);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(6b); or    -   C₆-C₁₀ aryl substituted with 0-3R^(6b);-   R^(6a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, phenyl or CF₃;-   R^(6b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, aryl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H and C₁-C₄ alkyl;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, 2, 3, or 4;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, 2, or 3;-   u is 0, 1, 2, or 3;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₆ alkyl or C₃-C₈ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or    —OC(═O)—;-   Z is C₁-C₄ alkyl substituted with 0-3 R^(12b);    -   C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;-   B is a 5 to 10 membered lactam or thiolactam,    -   wherein the lactam or thiolactam is saturated, partially        saturated or unsaturated;    -   wherein each additional lactam carbon or thiolactam carbon is        substituted with 0-2 R¹¹; and,    -   optionally, the lactam or thiolactam contains a heteroatom        selected from —O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-2 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or aryl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,    acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄    haloalkyl, C₁-C₄ haloalkoxy, and C₁-C₄ halothioalkoxy;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷,        C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(1b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄    haloalkoxy, and C₁-C₄ halothioalkoxy;-   R¹⁴, at each occurrence, is independently selected from H, phenyl,    benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R^(14a) is H, phenyl, benzyl, or C₁-C₄ alkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, aryl-CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[2] In a preferred embodiment the present provides

-   A is O;-   Q is —NR¹R²;-   R¹, at each occurrence, is independently selected from:    -   H;    -   C₁-C₆ alkyl substituted with 0-3 R^(1a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(1a);-   R^(1a), at each occurrence, is independently selected from H, OR¹⁴,    F, ═O, NR¹⁵R¹⁶, CF₃;    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(1b);    -   phenyl substituted with 0-3 R^(1b); and    -   5 to 6 membered heterocycle substituted with 0-3 R^(1b);-   R^(1b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R² is independently selected from H, NH₂, OH, C₁-C₆ alkyl, C₁-C₆    alkoxy, phenoxy, and benzyloxy;-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—NHC(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)NH—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—NHS(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—S(═O)₂NH—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, 2, or 3;-   m is 0, 1, 2, or 3;-   R^(3a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₂-C₄ alkenyloxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₁-C₆ alkoxy substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H;    -   C₁-C₆ alkyl substituted with 0-3 R^(6a);    -   C₃-C₆ carbocycle substituted with 0-3 R^(6b); or    -   C₆-C₁₀ aryl substituted with 0-3R^(6b);-   R^(6a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, phenyl or CF₃;-   R^(6b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, aryl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H and C₁-C₄ alkyl;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, 2, 3, or 4;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, 2, or 3;-   u is 0, 1, 2, or 3;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₆ alkyl or C₃-C₈ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or    —OC(═O)—;-   Z is C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   B is a 6, 7, or 8 membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-1 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from-   C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷,    C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[3] In a further preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a)) m-R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—N(R^(7b))-(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, or 2;-   m is 0, 1, or 2;-   R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, or butoxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H, methyl, or ethyl;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H, methyl, ethyl, propyl, and    butyl;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, or 2;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₃ alkyl, C₂-C₃ alkenyl, C₂-C₃ alkynyl and C₃-C₆    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, or 2;-   u is 0, 1, or 2;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;-   Z is C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   B is a seven membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-1 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from C₁-C₄    alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹,    S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[4] In a further preferred embodiment the present invention provides

-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;-   n is 0 or 1;-   m is 0 or 1;-   R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, or butoxy;-   R⁴ is H, OH,    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-1 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), phenyl substituted        with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, or allyl;-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   R⁶ is H;-   R⁷, at each occurrence, is independently selected from H, F, CF₃,    methyl, and ethyl;-   R^(7a), at each occurrence, is independently selected from H, F,    CF₃, methyl, and ethyl;-   R^(7b) is independently selected from H, methyl, and ethyl;-   W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   B is a seven membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷;    -   C₁-C₄ alkyl substituted with 0-1 R^(10a);    -   phenyl substituted with 0-4 R^(10b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(10b); or    -   5 to 6 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₄ alkyl, C₁-C₃ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃;    -   C₁-C₄ alkyl substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); or    -   5 to 6 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a cyclopropyl, cyclobutyl,    cyclopentyl, cyclohexyl, or a benzo fused radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁷ is H, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,    4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,    (4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,    propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, or    ethoxyethyl;-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl.

[5] In a more preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂ (CH₃)₂,    —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,    —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃,    -   —CH═CH₂, —CH₂CH═CH₂, —CH₂C(CH₃)═CH₂, —CH₂CH═C(CH₃)₂,        —CH₂CH₂CH═CH₂, —CH₂CH₂C(CH₃)═CH₂, —CH₂CH₂CH═C(CH₃)₂,        cis-CH₂CH═CH(CH₃), cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃),        trans-CH₂CH₂CH═CH(CH₃);    -   —C≡CH, —CH₂C═CH, —CH₂C≡C(CH₃),    -   cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,        cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,        cyclopentyl-CH₂CH₂—, cyclohexyl-CH₂CH₂—,    -   phenyl-CH₂—,    -   (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,        (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—,    -   (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,    -   (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,    -   (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,    -   (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,    -   (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,    -   (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,    -   (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,    -   (3-Cl-4-F-phenyl)CH₂—,    -   phenyl-CH₂CH₂—,    -   (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,    -   (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    -   (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,    -   (2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,    -   (2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,    -   (3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,    -   (2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,    -   (2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,    -   (3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,    -   (3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—, or-   R⁵ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₃)₂, —CH₂CH₂CH₂CH₃,    —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CH₂CH₂CH₂CH₂CH₃,    —CH(CH₃)CH₂CH₂CH₃, —CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂, —CH(CH₂CH₃)₂,    —CF₃, —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH₂CH₂CH₂CH₂CF₃, —CH═CH₂,    —CH₂CH═CH₂, —CH═CHCH₃, cis-CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃),    trans-CH₂CH═CH(C₆H₅), —CH₂CH═C(CH₃)₂, cis-CH₂CH═CHCH₂CH₃,    trans-CH₂CH═CHCH₂CH₃, cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH₂CH═CH(CH₃),    trans-CH₂CH═CHCH₂(C₆H₅), —C≡CH, —CH₂C≡CH, —CH₂C≡C(CH₃),    —CH₂C≡C(C₆H₅) —CH₂CH₂C≡CH, —CH₂CH₂C≡C(CH₃), —CH₂CH₂C≡C(C₆H₅)    —CH₂CH₂CH₂C≡CH, —CH₂CH₂CH₂CC(CH₃), —CH₂CH₂CH₂C(C₆H₅)    -   cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,        cyclohexyl-CH₂—, (2-CH₃-cyclopropyl)CH₂—, (3-CH₃-cyclobutyl)        CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,        cyclopentyl-CH₂CH₂—, cyclohexyl-CH₂CH₂—,        (2-CH₃-cyclopropyl)CH₂CH₂—, (3-CH₃-cyclobutyl)CH₂CH₂—,    -   phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,    -   (4-F-phenyl)CH₂—, furanyl-CH₂—, thienyl-CH₂—, pyridyl-CH₂—,        1-imidazolyl-CH₂—, oxazolyl-CH₂—, isoxazolyl-CH₂—,    -   phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,    -   (4-F-phenyl)CH₂CH₂—, furanyl-CH₂CH₂—, thienyl-CH₂CH₂—,        pyridyl-CH₂CH₂—, 1-imidazolyl-CH₂CH₂—, oxazolyl-CH₂CH₂—,    -   isoxazolyl-CH₂CH₂—,-   W is a bond, —CH₂—, or —CH(CH₃)—;-   X is a bond;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is phenyl 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,    3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,    2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,    2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,    3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,    3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl,    2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl,    4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl,    thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl,    1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, cyclopropyl,    cyclobutyl, cyclopentyl, cyclohexyl, morpholino, N-piperinyl,    phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,    (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—,    (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—,    (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,    (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—,    (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,    (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—, (3-Cl-4-F-phenyl)CH₂—,    (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—,    (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—,    (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—,    (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—,    (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-pipridinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl-4-F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, (N-pipridinyl)CH₂CH₂—,-   B is a seven membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,    (4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl,    (4-CH₃-phenyl)CH₂—, (4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl,    (4-CF₃-phenyl)CH₂—, or (4-CF₃-phenyl) CH₂CH₂—;-   R¹¹, at each occurrence, is independently selected from H, ═O,    methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,    (4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl,    (4-CH₃-phenyl)CH₂—, (4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl,    (4-CF₃-phenyl)CH₂—, or (4-CF₃-phenyl) CH₂CH₂—; and-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a cyclopropyl, cyclobutyl,    cyclopentyl, cyclohexyl, or a benzo fused radical.

[6] In a futher more preferred embodiment the present invention provides

-   B is

[7] In an even more preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is R⁴,-   R⁴ is C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),-   R^(4a), at each occurrence, is independently selected from is H, F,    CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   W is —CH₂—, or —CH(CH₃)—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹¹ is methoxy, ethoxy, propoxy, butoxy, Cl, F, ═O, NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); or    -   5 to 6 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a cyclopropyl, cyclobutyl,    cyclopentyl, cyclohexyl, or a benzo fused radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, butyl;-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl.

[8] In another even more preferred embodiment the present inventionprovides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is R⁴,-   R⁴ is C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),-   R^(4a), at each occurrence, is independently selected from is H, F,    CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), phenyl substituted        with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   W is —CH₂—, or —CH(CH₃)—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷;    -   C₁-C₄ alkyl substituted with 0-1 R^(10a);    -   phenyl substituted with 0-4 R^(10b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(10b); or    -   5 to 6 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, Cl, F, Br,    I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, butyl;-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl); and-   R¹⁷ is H, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,    4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,    (4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,    propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, or    ethoxyethyl.

[9] In another even more preferred embodiment the present inventionprovides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is R⁴,-   R⁴ is C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),-   R^(4a), at each occurrence, is independently selected from is H, F,    CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5C);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   W is —CH₂—, or —CH(CH₃)—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹¹ is methoxy, ethoxy, propoxy, butoxy, Cl, F, ═O, NR¹⁸R¹⁹, CF₃;    -   C₁-C₄ alkyl substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); or    -   5 to 6 membered heterocycle substituted with 0-3 R^(11b);-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, butyl;-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl;-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl.

[10] In another even more preferred embodiment the present inventionprovides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is R⁴,-   R⁴ is C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-1 R^(4a),-   R^(4a), at each occurrence, is independently selected from is H, F,    CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   W is —CH₂—, or —CH(CH₃)—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹⁴ is. H, phenyl, benzyl, methyl, ethyl, propyl, butyl;-   R¹⁵, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, and butyl; and-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl).

[11] In another preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, or 2;-   m is 0, 1, or 2;-   R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, or butoxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H, methyl, or ethyl;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H, methyl, ethyl, propyl, and    butyl;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, or 2;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₃ alkyl, C₂-C₃ alkenyl, C₂-C₃ alkynyl and C₃-C₆    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, or 2;-   u is 0, 1, or 2;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,    —N(R¹⁹)—C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;-   Z is C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   B is a seven membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-1 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,        C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[12] In a more preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is R⁴,-   n is 0 or 1;-   m is 0 or 1;-   R⁴ is H, OH,    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-1 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   B is a seven membered lactam,    -   wherein the lactam is saturated, partially saturated or        unsaturated;    -   wherein each additional lactam carbon is substituted with 0-2        R¹¹; and,    -   optionally, the lactam contains a heteroatom selected from —O—,        —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷;    -   C₁-C₄ alkyl substituted with 0-1 R^(10a);    -   phenyl substituted with 0-4 R^(10b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(10b); or    -   5 to 6 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₄ alkyl, C₁-C₃ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃;    -   C₁-C₄ alkyl substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); or    -   5 to 6 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a cyclopropyl, cyclobutyl,    cyclopentyl, cyclohexyl, or a benzo fused radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁷ is H, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,    4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,    (4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,    propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, or    ethoxyethyl;-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl.

[13] In an even more preferred embodiment the present invention provides

-   B is

[14] In a preferred embodiment the present provides

-   A is S;-   Q is —NR¹R²;-   R¹, at each occurrence, is independently selected from:    -   H;    -   C₁-C₆ alkyl substituted with 0-3 R^(1a);    -   C₂-C₆ alkenyl substituted with 0-3 R^(1a);-   R^(1a), at each occurrence, is independently selected from H, OR¹⁴,    F, ═O, NR¹⁵R¹⁶, CF₃;    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(1b);    -   phenyl substituted with 0-3 R^(1b); and    -   5 to 6 membered heterocycle substituted with 0-3 R^(1b);-   R^(1b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R² is independently selected from H, NH₂, OH, C₁-C₆ alkyl, C₁-C₆    alkoxy, phenoxy, and benzyloxy;-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a)) m-R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—NHC(═O)—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—C(═O)NH—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—NHS(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—S(═O)₂NH—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, 2, or 3;-   m is 0, 1, 2, or 3;-   R^(3a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₂-C₄ alkenyloxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₆ alkyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkenyl substituted with 0-3 R^(4a),    -   C₂-C₆ alkynyl substituted with 0-3 R^(4a),    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I, CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₁-C₆ alkoxy substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H;    -   C₁-C₆ alkyl substituted with 0-3 R^(6a);    -   C₃-C₆ carbocycle substituted with 0-3 R^(6b); or    -   C₆-C₁₀ aryl substituted with 0-3R^(6b);-   R^(6a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, phenyl or CF₃;-   R^(6b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, aryl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H and C₁-C₄ alkyl;-   W is (CR⁸R^(8a))_(p)—;-   p is 0, 1, 2, 3, or 4;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl and C₃-C₈    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, 2, or 3;-   u is 0, 1, 2, or 3;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₆ alkyl or C₃-C₈ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, —S(═O)NR^(19b)—, —C(═O)O—, or    —OC(═O)—;-   Z is C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   B is a 6, 7, or 8 membered thiolactam,    -   wherein the thiolactam is saturated, partially saturated or        unsaturated;    -   wherein each additional thiolactam carbon is substituted with        0-2 R¹¹; and,    -   optionally, the thiolactam contains a heteroatom selected from        —O—, —S—, —S(═O)—, —S(═O)₂—, and —-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-1 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷,        C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[15] In a further preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴;-   n is 0, 1, or 2;-   m is 0, 1, or 2;-   R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, or butoxy;-   R⁴ is H, OH, OR^(14a),    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, Br, I CF₃,    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₆ alkyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkenyl substituted with 0-3 R^(5b);    -   C₂-C₆ alkynyl substituted with 0-3 R^(5b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3R^(5c);-   R^(5a) is H, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄    alkenyloxy;-   R^(5b), at each occurrence, is independently selected from:    -   H, C₁-C₆ alkyl, CF₃, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶;    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(5c);    -   C₆-C₁₀ aryl substituted with 0-3 R^(5c); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   R⁶ is H, methyl, or ethyl;-   R⁷, at each occurrence, is independently selected from H, OH, Cl, F,    Br, I, CN, NO₂, CF₃, and C₁-C₄ alkyl;-   R^(7a), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;-   R^(7b) is independently selected from H, methyl, ethyl, propyl, and    butyl;-   W is —(CR⁸R^(8a))_(p)—;-   p is 0, 1, or 2;-   R⁸ and R^(8a), at each occurrence, are independently selected from    H, F, C₁-C₃ alkyl, C₂-C₃ alkenyl, C₂-C₃ alkynyl and C₃-C₆    cycloalkyl;-   X is a bond;    -   C₆-C₁₀ aryl substituted with 0-3 R^(Xb);    -   C₃-C₁₀ carbocycle substituted with 0-2 R^(Xb); or    -   5 to 10 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   Y is a bond or —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—;-   t is 0, 1, or 2;-   u is 0, 1, or 2;-   R⁹ and R^(9a), at each occurrence, are independently selected from    H, F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —N(R¹⁹)—,    —C(═O)NR^(19b)—, —NR^(19b)C(═O)—, —NR^(19b)S(═O)₂—,    —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;-   Z is C₁-C₃ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄    haloalkoxy;-   B is a seven membered thiolactam,    -   wherein the thiolactam is saturated, partially saturated or        unsaturated;    -   wherein each additional thiolactam carbon is substituted with        0-2 R¹; and,    -   optionally, the thiolactam contains a heteroatom selected from        —O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,    S(═O)₂R¹⁷;    -   C₁-C₆ alkyl substituted with 0-1 R^(10a);    -   C₆-C₁₀ aryl substituted with 0-4 R^(10b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(10b); or    -   5 to 10 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₆ alkyl, C₁-C₄ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷,        C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹, CF₃;    -   C₁-C₆ alkyl substituted with 0-1 R^(11a);    -   C₆-C₁₀ aryl substituted with 0-3 R^(11b);    -   C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a C₃-C₆ carbocycle or a benzo fused    radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₆    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-3 R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,    C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl);-   R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl;-   R¹⁸, at each occurrence, is independently selected from H, C₁-C₆    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆    alkyl); and-   R¹⁹, at each occurrence, is independently selected from H, OH, C₁-C₆    alkyl, phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and    —S(═O)₂—(C₁-C₆ alkyl); and-   R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or    phenethyl.

[16] In a further preferred embodiment the present invention provides

-   R³ is —(CR⁷R^(7a))_(n)—R⁴,    -   —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,    -   —(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or    -   —(CR⁷R^(7a))_(n)—N(R^(7b))-(CR⁷R^(7a))_(m)—R⁴;-   n is 0 or 1;-   m is 0 or 1;-   R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, or butoxy;-   R⁴ is H, OH,    -   C₁-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-1 R^(4a),    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   C₆-C₁₀ aryl substituted with 0-3 R^(4b), or    -   5 to 10 membered heterocycle substituted with 0-3 R^(4b);-   R^(4a), at each occurrence, is independently selected from is H, F,    Cl, CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), phenyl substituted        with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   R⁵ is H, OR¹⁴;    -   C₁-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,    propoxy, butoxy, or allyl;-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c);-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,    S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy;-   R⁶ is H;-   R⁷, at each occurrence, is independently selected from H, F, CF₃,    methyl, and ethyl;-   R^(7a), at each occurrence, is independently selected from H, F,    CF₃, methyl, and ethyl;-   R^(7b) is independently selected from H, methyl, and ethyl;-   W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);-   R^(Xb), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—,    or —N(CH₂CH₃)—,-   Z is C₁-C₂ alkyl substituted with 1-2 R¹²;    -   C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R¹² is C₆-C₁₀ aryl substituted with 0-4 R^(12b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(12b); or    -   5 to 10 membered heterocycle substituted with 0-3 R^(12b);-   R^(12b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl,    C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;-   B is a seven membered thiolactam,    -   wherein the thiolactam is saturated, partially saturated or        unsaturated;    -   wherein each additional thiolactam carbon is substituted with        0-2 R¹¹; and,    -   optionally, the thiolactam contains a heteroatom selected from        —O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, C(═O)R¹⁷, C(═O)OR¹⁷;    -   C₁-C₄ alkyl substituted with 0-1 R^(10a);    -   phenyl substituted with 0-4 R^(10b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(10b); or    -   5 to 6 membered heterocycle optionally substituted with 0-3        R^(10b);-   R^(10a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl    substituted with 0-4 R^(10b);-   R^(10b), at each occurrence, is independently selected from H, OH,    C₁-C₄ alkyl, C₁-C₃ alkoxy, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, or CF₃;-   R¹¹, at each occurrence, is independently selected from    -   C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃;    -   C₁-C₄ alkyl substituted with 0-1 R^(11a);    -   phenyl substituted with 0-3 R^(11b);    -   C₃-C₆ carbocycle substituted with 0-3 R^(11b); or    -   5 to 6 membered heterocycle substituted with 0-3 R^(11b);-   alternatively, two R¹¹ substituents on the same or adjacent carbon    atoms may be combined to form a cyclopropyl, cyclobutyl,    cyclopentyl, cyclohexyl, or a benzo fused radical;-   R^(11a), at each occurrence, is independently selected from H, C₁-C₄    alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3    R^(11b);-   R^(11b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl;-   R¹⁵, at each occurrence, is independently selected from H, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁶, at each occurrence, is independently selected from H, OH, C₁-C₄    alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄    alkyl);-   R¹⁷ is H, phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,    4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,    (4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,    propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, or    ethoxyethyl;-   R¹⁸, at each occurrence, is independently selected from H, methyl,    ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and-   R¹⁹, at each occurrence, is independently selected from H, methyl,    and ethyl.

[17] In a more preferred embodiment the present invention provides

-   or a pharmaceutically acceptable salt or prodrug thereof, wherein:-   R³ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂(CH₃)₂,    —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃,    —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH═CH₂, —CH₂CH═CH₂, —CH₂C(CH₃)═CH₂,    —CH₂CH═C(CH₃)₂, —CH₂CH₂CH═CH₂, —CH₂CH₂C(CH₃)═CH₂, —CH₂CH₂CH═C(CH₃)₂,    cis-CH₂CH═CH(CH₃), cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃),    trans-CH₂CH₂CH═CH(CH₃); —C═CH, —CH₂C≡CH, —CH₂C═C(CH₃),    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—,    cyclopentyl-CH₂CH₂—, cyclohexyl-CH₂CH₂—, phenyl-CH₂—,    (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,    (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—,    (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—,    (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,    (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—,    (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,    (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—, (3-Cl-4-F-phenyl)CH₂—,    phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,    (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—,    (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, or-   R⁵ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₃)₂, —CH₂CH₂CH₂CH₃,    —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CH₂CH₂CH₂CH₂CH₃,    —CH(CH₃)CH₂CH₂CH₃, —CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂, —CH(CH₂CH₃)₂,    —CF₃, —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH₂CH₂CH₂CH₂CF₃, —CH═CH₂,    —CH₂CH═CH₂, —CH═CHCH₃, cis-CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃),    trans-CH₂CH═CH(C₆H₅), —CH₂CH═C(CH₃)₂, cis-CH₂CH═CHCH₂CH₃,    trans-CH₂CH═CHCH₂CH₃, cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH₂CH═CH(CH₃),    trans-CH₂CH═CHCH₂(C₆H₅), —C═CH, —CH₂C≡CH, —CH₂C≡C(CH₃),    —CH₂C≡C(C₆H₅) —CH₂CH₂C≡CH, —CH₂CH₂C≡C(CH₃), —CH₂CH₂C≡C(C₆H₅)    —CH₂CH₂CH₂C≡CH, —CH₂CH₂CH₂C≡C(CH₃), —CH₂CH₂CH₂C≡C(C₆H₅)    cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,    cyclohexyl-CH₂—, (2-CH₃-cyclopropyl)CH₂—, (3-CH₃-cyclobutyl)CH₂—,    cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—, cyclopentyl-CH₂CH₂—,    cyclohexyl-CH₂CH₂—, (2-CH₃-cyclopropyl)CH₂CH₂—,    (3-CH₃-cyclobutyl)CH₂CH₂—, phenyl-CH₂—, (2-F-phenyl)CH₂—,    (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, furanyl-CH₂—, thienyl-CH₂—,    pyridyl-CH₂—, 1-imidazolyl-CH₂—, oxazolyl-CH₂—, isoxazolyl-CH₂—,    phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,    (4-F-phenyl)CH₂CH₂—, furanyl-CH₂CH₂—, thienyl-CH₂CH₂—,    pyridyl-CH₂CH₂—, 1-imidazolyl-CH₂CH₂—, oxazolyl-CH₂CH₂—,    isoxazolyl-CH₂CH₂—,-   W is a bond, —CH₂—, or —CH(CH₃)—;-   X is a bond;-   Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;-   V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, or    —N(CH₃)—,-   Z is phenyl 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,    3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,    2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,    2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,    3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,    3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl,    2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl,    4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, furanyl,    thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl, 4-Me-pyridyl,    1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl, cyclopropyl,    cyclobutyl, cyclopentyl, cyclohexyl, morpholino, N-piperinyl,    phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—,    (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—,    (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—,    (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—,    (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—,    (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—,    (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—, (3-Cl-4-F-phenyl)CH₂—,    (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—,    (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—,    (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—,    (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—,    (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—, (2-Me-pyridyl)CH₂—,    (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—, (1-imidazolyl)CH₂—,    (oxazolyl)CH₂—, (isoxazolyl)CH₂—, (1-benzimidazolyl)CH₂—,    (cyclopropyl)CH₂—, (cyclobutyl)CH₂—, (cyclopentyl)CH₂—,    (cyclohexyl)CH₂—, (morpholino)CH₂—, (N-pipridinyl)CH₂—,    phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—,    (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—,    (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—,    (2,4-diF-phenyl)CH₂CH₂—, (2,5-diF-phenyl)CH₂CH₂—,    (2,6-diF-phenyl)CH₂CH₂—, (3,4-diF-phenyl)CH₂CH₂—,    (3,5-diF-phenyl)CH₂CH₂—, (2,3-diCl-phenyl)CH₂CH₂—,    (2,4-diCl-phenyl)CH₂CH₂—, (2,5-diCl-phenyl)CH₂CH₂—,    (2,6-diCl-phenyl)CH₂CH₂—, (3,4-diCl-phenyl)CH₂CH₂—,    (3,5-diCl-phenyl)CH₂CH₂—, (3-F-4-Cl-phenyl)CH₂CH₂—,    (3-F-5-Cl-phenyl)CH₂CH₂—, (3-Cl-4-F-phenyl)CH₂CH₂—,    (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—, (4-MeO-phenyl)CH₂CH₂—,    (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—, (4-Me-phenyl)CH₂CH₂—,    (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—, (4-MeS-phenyl)CH₂CH₂—,    (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,    (4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,    (pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,    (4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,    (isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,    (cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,    (morpholino)CH₂CH₂—, (N-pipridinyl)CH₂CH₂—,-   B is a seven membered thiolactam,    -   wherein the thiolactam is saturated, partially saturated or        unsaturated;    -   wherein each additional thiolactam carbon is substituted with        0-2 R¹¹; and,    -   optionally, the thiolactam contains a heteroatom selected from        —O—, —S—, —S(═O)—, —S(═O)₂—, and —N(R¹⁰)—;-   R¹⁰ is H, methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,    (4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl,    (4-CH₃-phenyl)CH₂—, (4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl,    (4-CF₃-phenyl)CH₂—, or (4-CF₃-phenyl)CH₂CH₂—;-   R¹¹ at each occurrence, is independently selected from H, ═O,    methyl, ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl,    (4-F-phenyl)CH₂—, (4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl,    (4-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl,    (4-CH₃-phenyl)CH₂—, (4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl,    (4-CF₃-phenyl)CH₂—, or (4-CF₃-phenyl)CH₂CH₂—; and alternatively, two    R¹¹ substituents on the same or adjacent carbon atoms may be    combined to form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl,    or a benzo fused radical.

[18] In a futher more preferred embodiment the present inventionprovides

-   B is

[19] In another even more preferred embodiment the present inventionprovides compounds of Formula (I) selected from:

-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(4-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2S,3R)    N1-[(3S)-hexahydro-1-(3-(2-tetrazolylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(propyl)-3-(2-methylpropyl)-butanediamide;-   (2S,3R)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(propyl)-3-(2-methylpropyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(phenethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-((4-fluorophenyl)methyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(phenethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-((4-fluorophenyl)methyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(phenethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-((4-fluorophenyl)methyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopropylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclobutylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclopentylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[(3S)-hexahydro-1-(cyclohexylethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide.

[20] In another even more preferred embodiment the present inventionprovides compounds of Formula (I) selected from:

-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-S-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[1,3-dihydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3-dihydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[1,3-dihydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide.

[21] In another even more preferred embodiment the present inventionprovides compounds of Formula (I) selected from:

-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-phenoxybenzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-methoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(4-trifluoromethylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[(6,7-dihydro-5-(3-(4-methylphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2,4-dichlorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(3-(3-chloro-4-fluorophenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzophenon-3-yl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[6,7-dihydro-5-(3-(2-naphthyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide.-   (2R,3S)    N1-[6,7-dihydro-5-(benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(phenethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-((4-fluorophenyl)methyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclohexylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclohexylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(phenethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-((4-fluorophenyl)methyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclohexylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclohexylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(phenethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-((4-fluorophenyl)methyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-S-(cyclohexylmethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopropylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclobutylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[6,7-dihydro-5-(cyclopentylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[6,7-dihydro-5-(cyclohexylethyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide.

[22] In another even more preferred embodiment the present inventionprovides compounds of Formula (I) selected from:

-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-S-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopropylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclobutylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzophenon-3-yl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(cyclopentylmethyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(1,3,4,5-tetrahydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(phenethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-((4-fluorophenyl)methyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopentylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylmethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopropylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclobutylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclopentylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide;    and-   (2R,3S)    N1-[1,3,4,5-tetrahydro-1-(cyclohexylethyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide.

[23] In another even more preferred embodiment the present inventionprovides compounds of Formula (I) selected from:

-   (2R,3S)    N1-[(3S)-hexahydro-1-(3,3-diphenylpropyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(phenyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methoxy)-N-4-(methyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methoxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(amino)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(allyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(3-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(butyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(2-furylmethyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide;-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(cyclopentyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide;    and-   (2R,3S)    N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(cinnamyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide.

In another preferred embodiment of the present invention, Q is N(OH)H.

In another preferred embodiment of the present invention, Q is NH₂.

In another preferred embodiment

-   R³ is R⁴,-   R^(3a) is H, methyl, ethyl, propyl, or butyl;-   R⁴ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl-   R⁵ is C₁-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl-   R^(5a) is H, methyl, ethyl, propyl, or butyl; and-   the total number of carbon atoms in R³, R^(3a), R⁵ and R^(5a) equals    seven or more.

In another preferred embodiment

-   R³ is R⁴;-   R^(3a) is H;-   R⁴ is C₁-C₄ alkyl substituted with 1-2 R^(4a),-   R^(4a), at each occurrence, is independently selected from    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₂-C₄ alkyl substituted with 0-3 R^(5b);    -   C₂-C₄ alkenyl substituted with 0-2 R^(5b); or    -   C₂-C₄ alkynyl substituted with 0-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴, ═O;    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c); and-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy.

In another preferred embodiment

-   R³ is R⁴;-   R^(3a) is H;-   R⁴ is C₂-C₄ alkyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkenyl substituted with 0-2 R^(4a),    -   C₂-C₄ alkynyl substituted with 0-2 R^(4a),-   R^(4a), at each occurrence, is independently selected from is H, F,    CF₃,    -   C₃-C₆ cycloalkyl substituted with 0-3 R^(4b),    -   phenyl substituted with 0-3 R^(4b), or    -   5 to 6 membered heterocycle substituted with 0-3 R^(4b);-   R^(4b), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy;-   R⁵ is C₁-C₄ alkyl substituted with 1-2 R^(5b);-   R^(5b), at each occurrence, is independently selected from:    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);    -   phenyl substituted with 0-3 R^(5c); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(5c); and-   R^(5c), at each occurrence, is independently selected from H, OH,    Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl,    ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and    C₁-C₂ haloalkoxy.

In another preferred embodiment

-   W is —(CH₂)_(p)—;-   p is 1, 2, or 3;-   X is a bond;    -   phenyl substituted with 0-2 R^(Xb);    -   C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or    -   5 to 6 membered heterocycle substituted with 0-2 R^(Xb);    -   wherein the 5 to 6 membered heterocycle does not contain an oxo        or imino substitued ring atom; and-   R^(Xb) at each occurrence, is independently selected from H, OH, Cl,    F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,    propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂    haloalkoxy.

In another preferred embodiment when R¹ is H, R² is hydroxy, and R¹¹ isH, then X is not a bond.

It is understood that any and all embodiments of the present inventionmay be taken in conjunction with any other embodiment to descibeadditional even more preferred embodiments of the present invention.

In a second embodiment, the present invention provides a pharmaceuticalcomposition comprising a compound of Formula (I) and a pharmaceuticallyacceptable carrier.

In a third embodiment, the present invention provides a method for thetreatment of neurological disorders associated with β-amyloid productioncomprising administering to a host in need of such treatment atherapeutically effective amount of a compound of Formula (I).

In a preferred embodiment the neurological disorder associated withβ-amyloid production is Alzheimer's Disease.

In a fourth embodiment, the present invention provides a method for thetreatment of neurological disorders associated with β-amyloid productioncomprising administering to a host in need of such treatment atherapeutically effective amount of a metalloprotease inhibitor whichinhibits γ-secretase activity.

In a preferred embodiment the neurological disorder associated withβ-amyloid production is Alzheimer's Disease.

In a preferred embodiment, the metalloprotease inhibitor is a hydroxamicacid.

In a more preferred embodiment, the metalloprotease inhibitor is ahydroxamic acid with an IC₅₀ value of less than 10 μM in the Aβimmunoprecipitation assay.

In a fifth embodiment, the present invention provides a method forinhibiting γ-secretase activity for the treatment of a physiologicaldisorder associated with inhibiting γ-secretase activity comprisingadministering to a host in need of such inhibition a therapeuticallyeffective amount of a compound of Formula (I) that inhibits γ-secretaseactivity.

In a preferred embodiment the physiological disorder associated withinhibiting γ-secretase activity is Alzheimer's Disease.

In a sixth embodiment, the present invention provides a compound ofFormula (I) for use in therapy.

In a preferred embodiment the present invention provides a compound ofFormula (I) for use in therapy of Alzheimer's Disease.

In a seventh embodiment, the present invention provides for the use of acompound of Formula (I) for the manufacture of a medicament for thetreatment of Alzheimer's Disease.

Definitions

As used herein, the term “Aβ” denotes the protein designated Aβ,β-amyloid peptide, and sometimes β/A4, in the art. Aβ is anapproximately 4.2 kilodalton (kD) protein of about 39 to 43 amino acidsfound in amyloid plaques, the walls of meningeal and parenchymalarterioles, small arteries, capillaries, and sometimes, venules. Theisolation and sequence data for the first 28 amino acids are describedin U.S. Pat. No. 4,666,829. The 43 amino acid sequence is: 1 Asp \Ala\Glu \Phe \Arg \His \Asp \Ser \Gly \Tyr 11 Glu \Val \His \His \Gln \Lys\Leu \Val \Phe \Phe 21 Ala \Glu \Asp \Val \Gly \Ser \Asn \Lys \Gly \Ala31 Ile \Ile \Gly \Leu \Met \Val \Gly \Gly \Val \Val 41 Ile \Ala \Thr.However, a skilled artisan knows that fragments generated by enzymaticdegradation can result in loss of amino acids 1-10 and/or amino acids39-43. Thus, an amino acid sequence 1-43 represents the maximum sequenceof amino acids for Aβ peptide.

The term “APP”, as used herein, refers to the protein known in the artas b amyloid precursor protein. This protein is the precursor for Aβ andthrough the activity of “secretase” enzymes, as used herein, it isprocessed into Aβ. Differing secretase enzymes, known in the art, havebeen designated b secretase, generating the N-terminus of Aβ, asecretase cleaving around the 16/17 peptide bond in Aβ, and “γsecretases”, as used herein, generating C-terminal Aβ fragments endingat position 38, 39, 40, 41, 42, and 43 or generating C-terminal extendedprecursors which are subsequently truncated to the above polypeptides.

The compounds herein described may have asymmetric centers. Compounds ofthe present invention containing an asymmetrically substituted atom maybe isolated in optically active or racemic forms. It is well known inthe art how to prepare optically active forms, such as by resolution ofracemic forms or by synthesis from optically active starting materials.Many geometric isomers of olefins, C═N double bonds, and the like canalso be present in the compounds described herein, and all such stableisomers are contemplated in the present invention. Cis and transgeometric isomers of the compounds of the present invention aredescribed and may be isolated as a mixture of isomers or as separatedisomeric forms. All chiral, diastereomeric, racemic forms and allgeometric isomeric forms of a structure are intended, unless thespecific stereochemistry or isomeric form is specifically indicated.

The term “substituted,” as used herein, means that any one or morehydrogens on the designated atom is replaced with a selection from theindicated group, provided that the designated atom's normal valency isnot exceeded, and that the substitution results in a stable compound.When a substituent is keto (i.e., ═O), then 2 hydrogens on the atom arereplaced.

When any variable (e.g., R^(5b)) occurs more than one time in anyconstituent or formula for a compound, its definition at each occurrenceis independent of its definition at every other occurrence. Thus, forexample, if a group is shown to be substituted with 0-2 R^(5b), thensaid group may optionally be substituted with up to two R^(5b) groupsand R^(5b) at each occurrence is selected independently from thedefinition of R^(5b). Also, combinations of substituents and/orvariables are permissible only if such combinations result in stablecompounds.

When a bond to a substituent is shown to cross a bond connecting twoatoms in a ring, then such substituent may be bonded to any atom on thering. When a substituent is listed without indicating the atom via whichsuch substituent is bonded to the rest of the compound of a givenformula, then such substituent may be bonded via any atom in suchsubstituent. Combinations of substituents and/or variables arepermissible only if such combinations result in stable compounds.

As used herein, “alkyl” or “alkylene” is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupshaving the specified number of carbon atoms; for example, “C₁-C₆ alkyl”denotes alkyl having 1 to 6 carbon atoms. Examples of alkyl include, butare not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl,sec-butyl, t-butyl, pentyl, and hexyl. Preferred “alkyl” group, unlessotherwise specified, is “C₁-C₄ alkyl”.

As used herein, “alkenyl” or “alkenylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more unsaturated carbon-carbon bonds which may occur in anystable point along the chain. Examples of “C₂-C₆ alkenyl” include, butare not limited to, ethenyl, 1-propenyl, 2-propenyl, 1-butenyl,2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 2-pentenyl, 3-pentenyl,hexenyl, and the like.

As used herein, “alkynyl” or “alkynylene” is intended to includehydrocarbon chains of either a straight or branched configuration andone or more carbon-carbon triple bonds which may occur in any stablepoint along the chain, such as ethynyl, 1-propynyl, 2-propynyl,1-butynyl, 2-butynyl, 3-butynyl, and the like.

“Alkoxy” or “alkyloxy” represents an alkyl group as defined above withthe indicated number of carbon atoms attached through an oxygen bridge.Examples of alkoxy include, but are not limited to, methoxy, ethoxy,n-propoxy, i-propoxy, n-butoxy, s-butoxy, t-butoxy, n-pentoxy, ands-pentoxy. Preferred alkoxy groups are methoxy, ethoxy, n-propoxy,i-propoxy, n-butoxy, s-butoxy, t-butoxy. Similarly, “alkylthio” or“thioalkoxy” is represents an alkyl group as defined above with theindicated number of carbon atoms attached through a sulphur bridge.

“Halo” or halogen as used herein refers to fluoro, chloro, bromo, andiodo. Unless otherwise specified, preferred halo is fluoro and chloro.“Counterion” is used to represent a small, negatively charged speciessuch as chloride, bromide, hydroxide, acetate, sulfate, and the like.

“Haloalkyl” is intended to include both branched and straight-chainsaturated aliphatic hydrocarbon groups having the specified number ofcarbon atoms, substituted with 1 or more halogen (for example—C_(v)F_(w) where v=1 to 3 and w=1 to (2v+1)). Examples of haloalkylinclude, but are not limited to, trifluoromethyl, trichloromethyl,pentafluoroethyl, pentachloroethyl, 2,2,2-trifluoroethyl,2,2-difluoroethyl, heptafluoropropyl, and heptachloropropyl.“Haloalkoxy” is intended to mean a haloalkyl group as defined above withthe indicated number of carbon atoms attached through an oxygen bridge;for example trifluoromethoxy, pentafluoroethoxy, 2,2,2-trifluoroethoxy,and the like. “Halothioalkoxy” is intended to mean a haloalkyl group asdefined above with the indicated number of carbon atoms attached througha sulphur bridge.

“Cycloalkyl” is intended to include saturated ring groups, having thespecified number of carbon atoms. For example, “C₃-C₆ cycloalkyl”denotes such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl.

As used herein, “carbocycle” is intended to mean any stable 3- to7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic ortricyclic, any of which may be saturated, partially unsaturated, oraromatic. Examples of such carbocycles include, but are not limited to,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,adamantyl, cyclooctyl, [3.3.0]bicyclooctane, [4.3.0]bicyclononane,[4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl,naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).Preferred “carbocycle” are cyclopropyl, cyclobutyl, cyclopentyl, andcyclohexyl.

As used herein, the term “heterocycle” or “heterocyclic ring” isintended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7-to 14-membered bicyclic heterocyclic ring which is saturated partiallyunsaturated or unsaturated (aromatic), and which consists of carbonatoms and 1, 2, 3 or 4 heteroatoms, preferably 1, 2, or 3 heteroatoms,independently selected from the group consisting of N, O and S andincluding any bicyclic group in which any of the above-definedheterocyclic rings is fused to a benzene ring. The nitrogen and sulfurheteroatoms may optionally be oxidized. The heterocyclic ring may beattached to its pendant group at any heteroatom or carbon atom whichresults in a stable structure. The heterocyclic rings described hereinmay be substituted on carbon or on a nitrogen atom if the resultingcompound is stable. If specifically noted, a nitrogen in the heterocyclemay optionally be quaternized. It is preferred that when the totalnumber of S and O atoms in the heterocycle exceeds 1, then theseheteroatoms are not adjacent to one another. It is preferred that thetotal number of S and O atoms in the heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, 1H-indazole,2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl,4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 61-1,2,5-thiadiazinyl,acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl,benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl,benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl,carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl,cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl,imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl,indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl,isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl,morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl,1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxazolidinylperimidinyl,phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl,phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl,piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl,purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl,pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl,pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl,quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl,tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl,6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl,1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl,thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl,triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl,1,3,4-triazolyl, xanthenyl. Preferred 5 to 10 membered heterocyclesinclude, but are not limited to, pyridinyl, pyrimidinyl, triazinyl,furanyl, thienyl, thiazolyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl,isoxazolyl, tetrazolyl, benzofuranyl, benzothiofuranyl, indolyl,benzimidazolyl, 1H-indazolyl, oxazolidinyl, isoxazolidinyl,benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, quinolinyl,and isoquinolinyl. Preferred 5 to 6 membered heterocycles include, butare not limited to, pyridinyl, pyrimidinyl, triazinyl, furanyl, thienyl,thiazolyl, pyrrolyl, piperazinyl, piperidinyl, pyrazolyl, imidazolyl,oxazolyl, isoxazolyl, tetrazolyl; more preferred 5 to 6 memberedheterocycles include, but are not limited to, pyridinyl, pyrimidinyl,triazinyl, furanyl, thienyl, thiazolyl, piperazinyl, piperidinyl,pyrazolyl, imidazolyl, and tetrazolyl. Also included are fused ring andspiro compounds containing, for example, the above heterocycles.

As used herein, the term “aryl”, “C₆-C₁₀ aryl” or aromatic residue, isintended to mean an aromatic moiety containing the specified number ofcarbon atoms; for example phenyl, pyridinyl or naphthyl. Unlessotherwise specified, “aryl” may be unsubstituted or substituted with 0to 3 groups selected from H, OH, OCH₃, Cl, F, Br, I, CN, NO₂, NH₂,N(CH₃)H, N(CH₃)₂, CF₃, OCF₃, C(═O)CH₃, SCH₃, S(═O)CH₃, S(═O)₂CH₃, CH₃,CH₂CH₃, CO₂H, and CO₂CH₃.

The phrase “additional lactam carbons and thiolactam carbons”, as usedherein, is intended to denote the number of optional carbon atoms in thelactam ring or thiolactam ring B of Formula (I). Formula (I″):

represents the lactam ring B of Formula (I). The ring numbering shownfor lactams of Formula (I″) applies to analogous thiolactams. Additionallactam carbons are carbons in lactam ring B other than the carbonsnumbered 2 and 3 in the backbone of the formula. The additional lactamcarbons may be optionally replaced by a heteroatom selected from oxygen,nitrogen and sulfur. Lactam ring B contains 1, 2, 3, 4, 5, 6 or 7optional carbons, wherein one optional carbon may optionally be replacedby a heteroatom, such that the total number of members of lactam ring B,including atoms numbered 1, 2 and 3 in the backbone, does not exceed 10.It is preferred that the total number of atoms of lactam ring B is 6, 7or 8; it is more preferred that the total number of atoms of lactam ringB is seven. Examples of lactam ring B include:

and their thiolactam counterparts. The examples are not intended tolimit the invention. Preferred examples of lactam ring B are B1, B2, B5,B6, B8, B9, B13, and B16; more preferred examples of lactam ring B areB1, B6, B8, B9, and B13. Preferred examples of substituent R¹⁰ or R¹¹ onlactam B are methyl, ethyl, phenyl, 4-fluorophenyl, 4-chlorophenyl,4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl, and(4-trifluorophenyl)methyl.

The compounds herein described may have asymmetric centers. Oneenantiomer of a compound of Formula (I) may display superior chemicalactivity over the opposite enantiomer. For example carbon 3 of lactamring B Formula (I″) may exist in either an S or R configuration. Thus,an R or S configuration at carbon 3 in Formula (I″) is considered partof the invention. An example of such configuration includes,

but is not intended to be limited to this example of ring B. Whenrequired, separation of the racemic material can be achieved by methodsknown in the art. Additionally, the carbon atoms to which R³ and R⁵ areattached may describe chiral carbons which may display superior chemicalactivity over the opposite enantiomer. For example, where R³ and R⁵ arenot H, then the configuration of the two centers may be described as(2R,3R), (2R,3S), (2S,3R), or (2S,3S). All configurations are consideredpart of the invention; however, the (2R,3S) and the (2S,3R) arepreferred and the (2R,3S) is more preferred.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

As used herein, “pharmaceutically acceptable salts” refer to derivativesof the disclosed compounds wherein the parent compound is modified bymaking acid or base salts thereof. Examples of pharmaceuticallyacceptable salts include, but are not limited to, mineral or organicacid salts of basic residues such as amines; alkali or organic salts ofacidic residues such as carboxylic acids; and the like. Thepharmaceutically acceptable salts include the conventional non-toxicsalts or the quaternary ammonium salts of the parent compound formed,for example, from non-toxic inorganic or organic acids. For example,such conventional non-toxic salts include those derived from inorganicacids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric,nitric and the like; and

the salts prepared from organic acids such as acetic, propionic,succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic,pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic,salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic,methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound which contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, nonaqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, Pa.,1985, p. 1418, the disclosure of which is hereby incorporated byreference.

“Prodrugs” are intended to include any covalently bonded carriers whichrelease the active parent drug according to formula (I) in vivo whensuch prodrug is administered to a mammalian subject. Prodrugs of acompound of formula (I) are prepared by modifying functional groupspresent in the compound in such a way that the modifications arecleaved, either in routine manipulation or in vivo, to the parentcompound. Prodrugs include compounds of formula (I) wherein a hydroxy,amino, or sulfhydryl group is bonded to any group that, when the prodrugor compound of formula (I) is administered to a mammalian subject,cleaves to form a free hydroxyl, free amino, or free sulfhydryl group,respectively. Examples of prodrugs include, but are not limited to,acetate, formate and benzoate derivatives of alcohol and aminefunctional groups in the compounds of formula (I), and the like.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent.

Synthesis

The compounds of the present invention can be prepared in a number ofways well known to one skilled in the art of organic synthesis. Thecompounds of the present invention can be synthesized using the methodsdescribed below, together with synthetic methods known in the art ofsynthetic organic chemistry, or variations thereon as appreciated bythose skilled in the art. Preferred methods include, but are not limitedto, those described below. All references cited herein are herebyincorporated in their entirety herein by reference.

The novel compounds of this invention may be prepared using thereactions and techniques described in this section. The reactions areperformed in solvents appropriate to the reagents and materials employedand are suitable for the transformations being effected. Also, in thedescription of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including choice ofsolvent, reaction atmosphere, reaction temperature, duration of theexperiment and workup procedures, are chosen to be the conditionsstandard for that reaction, which should be readily recognized by oneskilled in the art. It is understood by one skilled in the art oforganic synthesis that the functionality present on various portions ofthe molecule must be compatible with the reagents and reactionsproposed. Such restrictions to the substituents which are compatiblewith the reaction conditions will be readily apparent to one skilled inthe art and alternate methods must then be used.

Methods for the synthesis of succinylamino lactams are known in the artand are disclosed in a number of references including PCT publicationnumber WO 96/29313, which is hereby incorporated by reference.

Disubstituted succinate derivatives can be prepared by a number of knownprocedures. The procedure of Evans (D. A. Evans et al, Org. Synth. 86, p83 (1990)) is outlined in Scheme 1 where acylation of an oxazolidinonewith an acylating agent such as an acid chloride provides structures 1.Alkylation to form 2 followed by cleavage of the chiral auxiliary andsubsequent alkylation of the dianion of the carboxylic acid 3 provides avariety of disubstituted succinates which can be separated andincorporated into structures of Formula (I) by those skilled in the art.Additional examples are found in P. Becket, M. J. Crimmin, M. H. Davis,Z. Spavold, Synlett, (1993), 137-138, incorporated herein by reference.

Diastereomerically pure succinate derivatives can be accessed using thechemistry outlined below, adapted from P. Becket, M. J. Crimmin, M. H.Davis, Z. Spavold, Synlett, (1993), 137-138 incorporated herein byreference. This reference provides the synthesis below to obtaincompound 9. Compound 11 is used as an intermediate and is prepared from9 by hydrogenation of the allyl group followed by coupling of9-fluorenemethanol under standard conditions using DCC and DMAP inCH₂Cl₂. Deprotection of the tert-butyl ester is accomplished bytreatment with 50% trifluoroacetic acid.

Additional methods useful for the preparation of succinate derivativesare known by those skilled in the art. Such references include, McClureand Axt, Bioorganic & Medicinal Chemistry Letters, 8 (1998) 143-146;Jacobson and Reddy, Tetrahedron Letters, Vol 37, No. 46, 8263-8266(1996); Pratt et al., SYNLETT, May 1998, p. 531; WO 97/18207; and WO98/51665. The synthetic disclosures of WO97/18207 and WO 98/51665 arehereby incorporated by reference.

A variety of compounds of Formula (I) can be prepared by methodsdescribed in Scheme 4. The protected α-amine 3 of theα-amino-ε-caprolactam can be prepared by methods well known in theliterature for amino protecting groups as discussed in Theodora W.Greene's book “Protective Groups in Organic Synthesis”, like N-Boc usingdi-t-butyldicarbonate in an appropriate solvent like DMSO. A sulfur atomcan be introduced into the ring providing L-α-amino-β-thio-ε-caprolactamaccording to the procedure in S. A. Ahmed et al, FEBS Letters, (1984),vol. 174, pages 76-9 (Scheme 3). One skilled in the art can extend thismethodology to the synthesis of β-amino and oxygen containing rings byanalogy. The sulfur-containing molecules can also be oxidized to thesulfoxide and sulfone by methods known to one skilled in the art.

The lactam nitrogen of compound 13 can be alkylated by generating theanion with bases such as LDA, lithium bis(trimethylsilyl)amide or sodiumhydride in solvents like THF, with or without cosolvents such as DMPU orHMPA and reacting this with a variety of groups containing leavinggroups (X″) like bromide, iodide, mesylate or tosylate. Alkylatingagents such as α-bromo amides, ketones and acids can be prepared by anumber of literature methods including halogenation of amino acids bydiazotization or are commercially available. Other suitable alkylatingagents such as alkyl, allylic and benzylic halides can be formed form avariety of precursors such as free-radical addition of halides oractivation of alcohols, and other chemistries known to those skilled inthe art. For discussion of these types of reactions, see Carey, F. A.and Sundberg, R. J., Advanced Organic Chemistry, Part A, New York:Plenum Press, 1990, pages 304-305, 342-347, 695-698.

The N-Boc protecting group can be removed by any number of methods wellknown in the literature like TFA in methylene chloride to give thecompound 15. The amine 15 can be coupled to an appropriately substitutedcarboxylic acid or acid chloride by methods well described in theliterature for making amide bonds, like TBTU in DMF with a base like NMMto give the elaborated compound 16. Compounds 16 can be alkylated usingstandard bases like LDA, NaH, or NaHMDS to deprotonate the amidefollowed by addition of an alkylating agent with an appropriate leavinggroup like halide, mesylate, or triflate in an appropriate solvent toprovide compounds 17 with an R⁶ substituent. The t-butyl ester is thenremoved by treatment with TFA in ethylene chloride to give thecarboxylic acid 17.

The final compounds 18 were prepared by treating the activatedcarboxylic acid of 17 with an appropriately substituted amine. Forinstance, activation of the carboxylic acid with HATU(O-(7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluroniumhexafluorophosphate) or PyBOP(benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoniumhexafluorophosphate) or other coupling agents known to those skilled inthe art allows condensation with ammonia to form primary amides.Similarly, condensation of the activated acid with hydroxylaminehydrochloride provides the hydroxamic acid, or reaction with a primaryor secondary amine provides the substituted amine derivative.

Activation of the acid with PyBrOP (bromo-tris-pyrrolidino-phosphoniumhexafluorophosphate) followed by addition of an alcohol and4-dimethylaminopyridine allows formation of the ester directly. Foradditional acylation reactions see for example Carey, F. A. andSundberg, R. J., Advanced Organic Chemistry, Part A, New York: PlenumPress, 1990, pages 475-479.

Additional Examples of compounds of Formula (I) can be prepared as shownin Scheme 5. A suitable resin for solid phase synthesis such as Fmoc(Fluorenylmethylcarbonyl)-protected hydroxylamine bound to polystyrenebeads can be purchased from Novabiochem, Inc. Deprotection of the Fmocgroup under standard conditions using 20% piperidine in DMF providestrityl-linked hydroxylamine resin. Coupling of afluorenylmethyl-protected succinic acid derivative such as 20 with acoupling agent such as HATU in a suitable solvent like DMF orN-methylpyrrolidinone provides the support-bound hydroxamate 21. TheFluorenylmethyl ester can be removed using 20% piperidine in DMF toprovide the free carboxylic acid which can be coupled to amines like thecaprolactam 22 (which is available using chemistry outlined in Scheme 4)using PyBOP (benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphoniumhexafluorophosphate) and a suitable base like DIEA in DMF or NMP. Thesupport-bound intermediate 23 can then be elaborated to biarylstructures of the type 24 using typical Suzuki coupling conditionsemploying a catalyst such as Palladium complexes liketetrakis(triphenylphosphine)-palladium with 2M aqueous sodium carbonateas a base in a suitable solvent like THF or DME and an excess of aboronic acid. The final compounds are liberated from the supportemploying dilute (5%) trifluoroacetic acid in CH₂CL₂ and purified byconventional chromatography.

General Procedure for Solid-Phase Synthesis According to Scheme 5.

Resin 20 of Scheme 5: Fmoc-protected resin 19 (2.0 g, 0.78 mmol/g, 1.56mmol) is purchased from Novabiochem and swelled in 20 ml of CH₂Cl₂ for 1hour. The CH₂Cl₂ is removed and the resin is then treated with 25% v/vpiperidine in DMF (8 mL) and allowed to shake slowly for 16 h. Thesolvent was removed by filtration and the resin was shaken with anadditional 8 mL of 25% v/v piperidine in DMF for 2 h at rt. The solventswere removed by filtration, and the resin 20 was rinsed 3× with 20 mL ofDMF, 3× with 20 mL of methanol, and 3× with 20 mL of CH₂Cl₂ and dried invacuo.

Succinate 10 of Scheme 2: Succinate 9 is prepared according to theliterature procedure (P. Becket, M. J. Crimmin, M. H. Davis, Z. Spavold,Synlett, (1993), 137-138). Succinate 9 (17.8 g, 66 mmol) is dissolved in250 mL of ethyl acetate and placed in a Parr shaker bottle. To thesolution is added 890 mg of 5% palladium on carbon, and the bottle ispressurized to 40 psi with hydrogen gas and shaken for 2.5 h at rt. Thehydrogen is removed and the palladium catalyst is removed by filtrationthrough a pad of celite. Concentration of the ethyl acetate solutionprovides 17.5 g (98%) of succinate 10. No further purification isnecessary. MS (M-H)⁺=271.

Succinate 21 of Scheme 5: Succinate 10 (6.3 g, 23.1 mmol) is dissolvedin 125 mL of CH₂Cl₂ and 4.8 g (23.3 mmol) of dicyclohexylcarbodiimide isadded. The solution is stirred at rt for 30 min and then 4.6 g (23.4mmol) of 9-fluorenemethanol is added followed by 122 mg (1 mmol) of4-dimethylaminopyridine. After 5 h of stirring at rt, the reactionsolution was diluted with an additional 100 mL of CH₂Cl₂ and filteredthrough a pad of celite to remove precipitated dicyclohexylurea. Thesolution was then washed 3× with 50 mL of a 1N HCl solution, 3× with 50mL of a saturated sodium bicarbonate solution, and 2× with 50 mL ofbrine. The crude product was dried over MgSO₄ and soncentrated onto 15 gof silica gel. Chromatography eluting with a gradient of 2.5% to 5%ethyl acetate/hexanes provided 6.4 g (61%) of the diester as an oil. Thepurified diester (6.4 g 14.2 mmol) is then dissolved in 25 mL of CH₂Cl₂,25 mL of trifluoroacetic acid is added, and the reaction solution isstirred at rt for 2 h. The reaction solution is directly concentrated invacuo to an oil which is then redissolved in 25 mL of toluene andreconcentrated, followed by drying in vacuo to provide 6.3 g (98%) ofthe desired succinate 9 as an oil which solidifies on standing. MS(M+Na)⁺=471, (M+2Na)⁺=439.

Caprolactam 23 of Scheme 5: Boc-caprolactam 14 (5.0 g 21.9 mmol) isdissolved in 60 mL of THF and chilled to −78° C. To the chilled solutionis added 24 mL of a 1.0 M solution of lithium bis(trimethylsilyl)amidein THF, and the solution was brounght to 0° C. and stirred for 15 min.To the anion solution was added 6.5 g (22 mmol) of 3-iodobenzyl bromide(Aldrich) and the the solution was allowed to warm to rt and stirred for18 h. The reaction solution was diluted with 50 mL of water andextracted 3× with ethyl acetate. The combined organic layers were driedover MgSO₄ and concentrated in vacuo. The crude product was purified bychromatography eluting with a gradient of 5-20% ethyl acetate/hexanes toafford 7.0 g (72%) of the title compound as a white solid. MS(M+Na)⁺=467.

Resin 22 of Scheme 5: Resin 22 (2.0 g, 0.78 mmol/g, 1.56 mmol) wasswollen in 3 mL of DMF. In a separate flask, 1.85 g (4.68 mmol) ofsuccinate 21 was dissolved in 3 mL of DMF and 2.5 ml ofN,N-diisopropylethylamine (14 mmol) wsa added, followed by 1.81 g (4.68mmol) of HATU. The solution containing the active ester was added to theslurried resin and the reaction suspension was slowly shaken for 18 h.The resin was then washed 3× with 20 mL of DMF, 3× with 20 mL ofmethanol, and 3× with 20 mL of CH₂Cl₂. Loading of the resin wasdetermined by Fmoc quantitation to be 0.25 mmol/g, see Reddy, M. P.;Voelker, P. J. Int. J. Pept. Protein Res. 1998, 31, 345-348.

Resin 24 of Scheme 5: Resin 22 (2.0 g, 0.25 mmol/g, 0.5 mmol) wassuspended in 10 mL of 25% piperidine in DMF. The suspended resin wasshaken for 30 min at rt, and then the resin was washed 3× with 20 mL ofDMF, 3× with 20 mL of methanol, and 3× with 20 mL of CH₂Cl₂. Deprotectedresin (1.0 g, 0.25 mmol) was swollen in 2 mL of DMF. To the slurry wasadded 650 mg (1.25 mmol) of PyBOP and 217 mL (1.25 mmol) of DIEA.Separately, 443 mg (0.97 mmol) of caprolactam 23 was dissolved in 2 mLof DMF and 436 mL (2.5 mmol) of DIEA was added. The caprolactam solutionwas added to the resin slurry and the resin was mixed for 18 h at rt.The solvents were then removed and the coupling was repeated, withshaking at rt for 6 h. The resin was then washed 3× with 10 mL of DMF,3× with 10 mL of methanol, and 3× with 10 mL of CH₂Cl₂.

Products 25 of Scheme 5: A 70 mg (17.5 mmol) portion of resin 24 wassuspended in 1 mL of THF in a screw-cap vial. To the slurry was added aboronic acid (0.15 mmol), 150 mL of a 2 M solution of sodium carbonate,and 15 mg (13 mmol) of tetrakis(triphenylphosphine)palladium. The vialwas tightly closed and heated to 60° C. for 16 h using a dry heater on ashaker table. The solvents were then removed by filtration and the resinwas washed 3× with THF (2 mL), 3× with methanol (2 mL), 3× with water,and 3× with CH₂Cl₂. The resins were then placed in a glass vial andcleaved with 1 mL of 5% trifluoroacetic acid in CH₂Cl₂ for 30 min. Thesolution ws filtered off and the resin was washed with an additional 2mL of CH₂Cl₂ and the combined filtrates were evaporated to dryness toyield the crude products 25. The products were purified bychromatography eluting with 10-100% ethyl acetate in hexanes to yield13.0 to 6.0 mg (14-60%) of the final products.

Additional Examples of compounds of Formula (I) can be prepared as shownin Scheme 6. A suitable resin for solid phase synthesis such as Fmoc(Fluorenylmethylcarbonyl)-protected peptide amide linker(PAL)-derivatized polystyrene beads can be purchased from Perkin ElmerBiosystems, Inc. Deprotection of the Fmoc group under standardconditions using 20% piperidine in DMF provides the free benzylamine.Coupling of a succinic acid derivative such as 28 (which is availableusing chemistry outlined in Scheme 4) with a coupling agent such as HATUin a suitable solvent like DMF or N-methylpyrrolidinone provides thesupport-bound amide 29. The support-bound intermediate 29 can then beelaborated to biaryl structures of the type 24 using typical Suzukicoupling conditions employing a catalyst such as Palladium complexeslike tetrakis(triphenylphosphine)-palladium with 2M aqueous sodiumcarbonate as a base in a suitable solvent like THF or DME and an excessof a boronic acid. The final compounds are liberated from the supportemploying 50% trifluoroacetic acid in CH₂Cl₂ and can be purified byconventional chromatography or preparative HPLC.

General Procedure for Solid-Phase Synthesis According to Scheme 6

Resin 27 of Scheme 6: Fmoc-protected PAL resin 26 (0.80 g, 0.50 mmol/g,0.40 mmol) is purchased from Advanced Chemtech and swelled in 20 ml ofCH₂Cl₂ for 1 hour. The CH₂Cl₂ is removed and the resin is then treatedwith 25% v/v piperidine in DMF (6 mL) and allowed to shake slowly for 1h. The solvents were removed by filtration, and the resin 27 was rinsed3× with 20 mL of DMF, 3× with 20 mL of methanol, and 3× with 20 mL ofCH₂Cl₂. and dried in vacuo.

Acid 28 of Scheme 6: To a solution of 0.100 g (367 mmol) of succinate 10dissolved in 2.0 mL of dry DMF was added 0.120 mL (1.10 mmol) ofN-methylmorpholine. A second solution containing 0.139 g (0.403 mmol) ofcaprolactam 23 of Scheme 5 dissolved in 2.0 mL of DMF was then added. Tothe mixed solution was added 229 mg (0.440 mmol) of PyBop and thereaction solution was stirred for 16 h at rt. The reaction solution wasdiluted with water (20 mL) and extracted 3× with 100 mL of ethylacetate. The combined organic layers were dried with Na₂SO₄ andconcentrated under reduced pressure. The resulting oil was purified bychromatography eluting with a gradient of 5-20% ethyl acetate in hexanesto provide 0.195 g (0.360 mmol, 98%) of the tert-butyl ester of Acid 28(MS M+Na=621). The purified ester (0.195 g, 0.360 mmol) was dissolved in10 mL of 25% trifluoroacetic acid in CH₂Cl₂ and stirred for 2 h at rt.The solvents were removed under reduced pressure and the acid wasredissolved in 5 mL of toluene and reconcentrated 2× to remove residualTFA. The crude acid was found to be pure by ¹H NMR and was used inScheme 6 without further purification.

Resin 29 of Scheme 6. Resin 27 (800 mg, 0.40 mmol) was solvated in 4.0mL of dry DMF and and 0.63 mL (3.6 mmol) of diisopropylethylamine wasadded followed by a solution of Acid 28 dissolved in 4 mL of DMF. To theslurry was then added 0.465 g (1.2 mmol) of HATU and the slurry wasshaken for 26 h at rt. The solvents were removed by filtration, and theresin 29 was rinsed 3× with 20 mL of DMF, 3× with 20 mL of methanol, and3× with 20 mL of CH₂Cl₂. and dried in vacuo.

Products 30 of Scheme 6: A 75 mg (0.38 mmol/g, 28.8 mmol) portion ofresin 24 was suspended in 1 mL of THF in a screw-cap vial. To the slurrywas added a boronic acid (0.33 mmol), 150 mL of a 2 M solution of sodiumcarbonate, and 15 mg (13 mmol) of tetrakis(triphenylphosphine)palladium.The vial was tightly closed and heated to 60° C. for 16 h using a dryheater on a shaker table. The solvents were then removed by filtrationand the resin was washed 3× with THF (2 mL), 3× with methanol (2 mL), 3×with water, and 3× with CH₂Cl₂. The resins were then placed in a glassvial and cleaved with 1 mL of 5% trifluoroacetic acid in CH₂Cl₂ for 2 h.The solution was filtered off and the resin was washed with anadditional 2 mL of CH₂Cl₂ and the combined filtrates were evaporated todryness to yield the crude products 25. The products were purified bychromatography eluting with 10-100% ethyl acetate in hexanes to yield0.5 to 2.0 mg (14-60%) of the final products.

The internal phenyl ring can be exchanged for a pyridine ring usingchemistry outlined in Scheme 7. The chloromethyl pyidine 33 is preparedusing a known procedure reported in Nutaitis, Charles F.; Ledeboer, MarkW. Org. Prep. Proced. Int. (1992), 24(2), 143-6 Incorporated herein byreference. After freebasing the pyridine, alkylation with theBoc-caprolactam provides pyridine intermediate 34, which can beelaborated to the protected amide 35 with succinate 10. Substitution canthen be introduced using Suzuki methodology employing a palladium sourcesuch as tetrakis(triphenylphosphine)palladium(0) orbis(diphenylphosphinoferrocene)palladium(II) dichloride and a suitablebase such as sodium carbonate or triethylamine in a solvent such as THFor toluene containing 10% methanol. Stille chemistry is also possibleusing a suitable palladium source such astetrakis(triphenylphosphine)palladium(0) and an aryl or vinyl tinderivative in a solvent such as benzene, toluene, or xylenes. Thetert-butyl ester is then deprotected under standard acidic conditionsusing trifluoroacetic acid and the amide is formed under standardconditions to provide products 36.

General Procedure for Synthesis According to Scheme 7

The chloromethyl pyidine HCl salt 33 is prepared using a known procedurereported in Nutaitis, Charles F.; Ledeboer, Mark W. Org. Prep. Proced.Int. (1992), 24(2), 143-6.

Caprolactam 34: Pyridine HCl salt 33 (2.0 g, 8.3 mmol) is dissolved in50 mL of a saturated NaHCO₃ solution and the solution is extracted with30 mL of CH₂Cl₂ 3× followed by concentration of the organic layers toprovide the free base. Separately, 1.8 g (7.8 mmol) of caprolactam 13 isdissolved in 40 mL of dry THF and chilled to −78° C. To the solution wasadded 8.7 mL of a 1M solution of sodium bis(trimethylsilyl)amide. Thesolution was brought to 0° C. and stirred for 30 min. To the resultantanion was added a solution of 1.7 g (8.3 mmol) of pyridine 33 free basedissolved in 40 mL of THF. The resulting reaction solution was stirredat rt for 18 h and then heated to 50° C. and stirred an additional 3 h.The reaction solution was allowed to cool and then 50 mL of water wasadded and the aqueous layer was extracted 2× with 100 mL of ethylacteate. The combined organic layers were dried and concentrated underreduced pressure to provide the crude product which was purified bychromatography eluting with 20 to 100% ethyl acetate in hexanes toprovide 1.5 g (51%) of caprolactam 34 as an oil.

Amide 35: Caprolactam 34 (0.40 g, 1.0 mmol) is dissolved in 20 mL of 50%trifluoroacetic acid in CH₂Cl₂ and stirred at rt for 30 min. Thesolvents were then removed under reduced pressure and the resulting oilwas redissolved in 5 mL of toluene and reconcentrated to remove residualTFA. Separately, 0.270 g (1.0 mmol) of succinate 10 was dissolved in 5.0mL of dry DMF and 0.44 mL (4 mmol) of N-methylmorpholine was addedfollowed by 0.50 g (1.3 mmol) of HATU and the resulting solution wasstirred at rt for 30 min. The crude deprotected caprolactam from abovewas dissolved in 5.0 mL of dry DMF and added to the succinate solutionand the resulting solution was heated to 50° C. and stirred for 2 days.The solution was then diluted with 20 mL of water and extracted with 350 mL portions of ethyl acetate. The combined organic layers were driedand concentrated under reduced pressure to provide an oil which waspurified by chromatography eluting with 20 to 50% ethyl acetate inhexanes to provide 0.40 g (70%) of the Amide 35.

Additional examples can be prepared by the method shown in Scheme 8.Coupling of an amine onto a commercially available aldehyde-derivedresin 37 under conditions for reductive amination such as sodiumtris(acetoxy)borohydride in CH₂Cl₂ containing 1% acetic provides asupport-bound amine 38. The carboxylic acid 39 can then be coupled tothe support-bound amine generating an amide 40 which can be liberatedfrom the support employing trifluoroacetic acid in CH₂Cl₂.

General Procedure for Solid-Phase Synthesis According to Scheme 8

Resin 38 of Scheme 5: Aldehyde-derived resin 37 (200 mg, 0.5 mmol/g, 0.1mmol) is purchased from Perkin Elmer Biosystems and swelled in 3 ml ofCH₂Cl₂ for 1 hour. An amine (1.0 mmol), sodium tris(acetoxy)borohydride(106 mg, 0.5 mmol) and acetic acid (30 uL, 1%) are added and thereaction is shaken on a shaker table for 16 h at rt. The solvents wereremoved by filtration and the resin 38 was rinsed 3× with 20 mL of DMF,3× with 20 mL of methanol, and 3× with 20 mL of CH₂Cl₂. and dried invacuo.

Products 40 of Scheme 8: Carboxylic acid 39 (23 mg, 0.045 mmol),diisopropylethylamine (13 mL, 0.075 mmol) and HATU (17.1 mg, 0.045 mmol)were mixed in 0.5 mL of DMF for 30 min. Amine-derived resins 38 (30 mg,0.015 mmol) were then added and the suspension was shaken at rt for 16h. The solvents were removed by filtration and the resins were rinsed 3×with 20 mL of DMF, 3× with 20 mL of methanol, and 3× with 20 mL ofCH₂Cl₂. The isolated resins were then cleaved by the addition of 0.50 mLof trifluoroacetic acid. The product solutions were concentrated andredissolved in 0.5 mL of methanol and reconcentrated 2× to removeresidual TFA. Product yields ranged from 0-100% based on the structureof the amine.

The compounds of Formula (I) of the present invention can also beprepared from aminolactam or aminothiolactam 42 and succinic acidderivatives 1 using amide bond syntheses known in the art, includingmethods commonly used in peptide syntheses, such as HATU, TBTU, BOP,pyBOP, EDC, CDI, DCC, hydroxysuccinimide, mixed carboxylic anhydride,and phenyl ester mediated couplings, as illustrated in Scheme 9 for thesynthesis of aminolactam or aminothiolactam 43, an embodiment of thepresent invention.

Depending on the structure of the final product, it is appreciated bythose skilled in the art that protecting groups or precursorfunctionality convertable to the desired groups may be desireable.Protecting groups and their use in synthesis are described in Green andWuts, Protective Groups in Organic Synthesis, (Wiley 1991). The use ofprotecting groups is further illustrated in Scheme 10, in which thesuccinate half-ester 44 (Becket et al., Synlett 1993, 137-138) iscoupled to the aminobenzodiazepine 45 (Sherrill and Sugg, J. Org. Chem.1995, 60, 730-734; Bock et al., J. Med. Chem., 1993, 36, 4276-4292) togive ester 46, followed by conversion of the ester group to the primaryamide 47.

Methods for the synthesis of lactams as contemplated by the presentinvention in lactam ring B in Formula (I), including aminobenzodiazepines, are known in the art and are disclosed in a number ofreferences including PCT publication number WO 98/28268, which is herebyincorporated by reference. Additional references include Bock, et al, J.Org. Chem., 1987, 52, 3232-3239 and Sherrill et al, J. Org. Chem., 1995,60, 730-734; Walsh, D. A., Synthesis, September 1980, p. 677.

The synthesis of the thiolactams of the present invention (Formula (I),A=S) can be carried out using thiolactam intermediates (42, A=S), usingthe methods described above. The thiolactam intermediates may beprepared from suitably protected aminolactams employing methods known tothose skilled in the art, using, for example, Lawessson's reagent,P4S10, or related methods (see Taylor et al., Bioorg. Med. Chem. Lett.1997, 7 (4), 453-456; Schwarz et al., Tetrahedron, 1997, 53 (26),8795-8806; Achour et al., Synth. Commun. 1994, 24 (20), 2899-2905; Buegeet al., Arch. Pharm. 1994, 327 (2), 99-103; Levai, et al., Arch. Pharm.1992 (325 (11), 721-726; Duhammel et al., Tetrahedron Asymmetry 1991, 2(3), 203-206; Bodine et al., Synth. Commun. 1982, 12, 787). Deprotectionof the amine, coupling to an appropriate succinate derivative andelaboration of the distal succinic acid derivative provides the desiredthiolactams of the present invention.

EXAMPLES

Chemical abbreviations used in the Examples are defined as follows:“DMPU” for 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidone, “TBTU” forO-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate,and “BOP” for benzotriazol-1-yloxytris-(dimethylamino)phosphoniumhexafluorophosphate. It is understood that one skilled in the art candiscern compounds used in the synthesis of Examples of the invention maybe referred to by structure and number. For example, Resin 20 refers tothe resin of structure 20 in Scheme 5; succinate 9 refers to thestructure 9 found in Scheme 2 which is a succinate compound.

“HPLC” is an abbreviation used herein for high pressure liquidchromatography. Reverse-phase HPLC was carried out using a Vydac C-18column with gradient elution from 10% to 100% buffer B in buffer A(buffer A: water containing 0.1% trifluoroacetic acid, buffer B: 10%water, 90% acetonitrile containing 0.1% trifluoroacetic acid).

Example 1 (2R,3S)N1-[(3S)-hexahydro-1-(3,3-diphenylpropyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Step (1a): Di-tert-butyldicarbonate (10.2 g, 46.7 mmoles) was addedportion wise to a solution of L-(−)-α-amino-ε-caprolactam (5.0 g, 39.0mmoles) in dimethyl sulfoxide (30 mL). After 5 h at rt, the reaction waspartitioned between water (100 mL) and ethyl acetate. The combinedorganic extracts were washed successively with 1 M HCl (50 mL), brine,and dried (MgSO₄) and concentrated in vacuo. The residue wasrecrystallized in 1:1 v/v ether-hexanes, two crops yielded the desiredproduct (6.26 g, 70%) as white solid. MS (M+H-BOC)⁺=129.

Step (1b): Triphenylphosphine (3.0 g, 11.4 mmoles) and carbontetrabromide (3.75 g, 11.7 mmoles) were added successively to a cooled(0° C.) solution of 3,3-biphenyl-1-propanol (1.5 mL, 7.5 mmoles) indichloromethane (20 mL). After 1.5 hours at rt, the mixture wasconcentrated in vacuo. The residue was purified by flash chromatographyon silica gel (hexanes) to give the desired product (1.93 g, 93% yield)as a clear oil. MS (M-BrC₂H₄)⁺=167

Step (1c): A 1.0 M tetrahydrofuran solution of lithiumbis(trimethylsilyl)amide (1.3 mL) was added over 15 minutes to compoundof Step (1a) (0.29 g, 1.27 mmoles) in tetrahydrofuran (3 mL) and DMPU (2mL) at −78° C. The iodo compound prepared from compound (1b) (0.85 g,3.09 mmoles) by typical Finkelstein methodology, in tetrahydrofuran (4mL) was added and the reaction was allowed to warm to rt slowly. Thiswas stirred for 10 hours at ambient temperature, partitioned betweenwater and ethyl acetate. The combined organic extracts were washedsuccessively with water (20 mL), brine (20 mL), and dried (MgSO₄) andconcentrated in vacuo. The resulting residue was purified by silica gelcolumn (ethyl acetate:hexanes, 5:95 then ethyl acetate:hexanes, 15:85)to give the desired product (0.16 g, 30%). MS (M-Ot-Bu)⁺=349.

Step (1d): Trifluoroacetic acid (3 mL) was added to a solution ofcompound of Step (1c) (0.16 mg, 0.38 mmoles) in dichloromethane (9 mL).After 2 h at rt, the solvent was removed in vacuo. The residualtrifluoroacetic acid was removed by azeotrope with dichloromethane (50mL), toluene (50 mL), and dichloromethane (50 mL) successively to givethe desired product (0.17 g, 99%) as a yellow oil. MS (M+H)⁺=323.

Step (1e): 4-Methylmorpholine (0.6 mL, 5.46 mmoles) and TBTU (0.11 g,0.34 mmoles) were added to a solution of succinate acid (P. Becket, M.J. Crimmin, M. H. Davis, Z. Spavold, Synlett, (1993), 137-138) (0.085 g,0.31 mmoles) in N,N-dimethylformamide (3 mL). After 30 minutes at rt,the compound from step (1d) (0.17 g, 0.39 mmoles) was added to themixture. The reaction was stirred for 16 h at rt, then partitionedbetween 1 M HCl (20 mL) and ethyl acetate. The combined organic extractswere washed successively with saturated aqueous sodium bicarbonate (20mL), water (20 mL), brine (20 mL), dried (MgSO₄) and concentrated invacuo. The residue was purified by silica gel chromatography (ethylacetate:hexanes, 7:93 gradient to ethyl acetate:hexanes 25:75) to givethe desired product (120 mg, 67%) as a clear oil. MS (M+NH₄-Ot-Bu)⁺=521.

Step (1f): Trifluoroacetic acid (3 mL) was added to a solution ofcompound of Step (1e) (120 mg, 0.21 mmoles) in dichloromethane (9 mL).After 3 hours at rt, the mixture was concentrated in vacuo. The residualtrifluoroacetic acid was removed by azeotrope with toluene (1×50 mL) anddichloromethane (1×50 mL). The residue was triturated with Et₂O:Hexanes95:5, to give the desired product (75 mg, 70%) as a white solid. MS(M-H)-=519.

Step (1g): 4-Methylmorpholine (0.05 mL, 0.45 mmoles) and BOP (73 mg,0.17 mmoles) were added to a solution of compound of Step (1f) (60 mg,0.12 mmoles) in N,N-dimethylformamide (2 mL). Hydroxylamine (33 mg, 0.47mmoles) was added to the mixture, the reaction was stirred for 16 h atrt, was concentrated in vacuo, was acidified with trifluoroacetic acid,then purified by reverse phase HPLC on a Vydac C-18 column, to give thedesired hydroxamic acid as a white solid (45 mg, 75%). MS (M-H)⁻=534.

Example 2 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Step (2a): Triphenylphosphine (3.40 g, 13.0 mmoles) andcarbontetrabromide (4.20 g, 13.0 mmoles) were added successively to asolution of m-phenoxybenzyl alcohol (1.5 mL, 8.6 mmoles). After 4 h atrt the mixture was concentrated and was purified by silica gel column(hexanes, then ethyl acetate:hexanes, 5:95) to give the desired bromide(1.3 g, 57%) as a yellow oil. MS (M-Br)⁺=183.

Step (2b): A 1 M solution of lithium bis(trimethylsilyl)amide was addeddropwise to a solution of compound of Step (1a) (0.3 g, 1.31 mmoles) intetrahydrofuran (5 mL) at −78° C. After 30 minutes a solution ofcompound of Step (2a) (0.43 g, 1.63 mmoles) in tetrahydrofuran (4 mL)was added to the mixture dropwise. The reaction was allowed to come toambient temperature, stirred for 16 h, then partitioned between waterand ethyl acetate. The combined organic extracts were washedsuccessively with water (20 mL), brine (20 mL), dried (MgSO₄) andconcentrated in vacuo. The crude residue was purified by silica gelchromatography (ethyl acetate:hexanes, 5:95 then ethyl acetate:hexanes,15:85) to give the desired product (360 mg, 67%) as a clear oil. MS(M-Ot-Bu)⁺=337.

Step (2c): Trifluoroacetic acid (5 mL) was added to a solution ofcompound of Step (2b) in dichloromethane (15 mL). After 3 h at rt thesolution was concentrated in vacuo. The residual trifluoroacetic acidwas removed from residue by azeotrope with toluene (50 mL) thendichloromethane (30 mL) to yield the desired amine (390 mg, 99%) as aclear oil. MS (M+H)⁺=311.

Step (2d): Following a procedure analogous to the preparation of Step(1e), but using the compound from of Step (2c) (390 mg, 0.88 mmoles) theamide was prepared, The crude compound was purified by silica gelchromatography to give the desired product (0.38 g, 92%) as a yellowoil. MS (M-Ot-Bu)⁺=491.

Step (2e): Following a procedure analogous to the preparation of step(1f), but using the compound from Step (2d) (380 mg, 0.67 mmoles), thecarboxylic acid was prepared. The product was precipitated from ethylether with hexanes, to give the desired acid (227 mg, 66%) as a whitesolid. MS (M-H)-=507.

Step (2f): Following a procedure analogous to the preparation ofcompound of Step (1g), but using the compound from step (2e) (150 mg,0.29 mmoles) the title compound was prepared. The crude was purified byreverse phase HPLC on a Vydac C-18 column to give the desired product(90 mg, 58%) as a white solid. MS (M-H)-=522.

Example 3 (2R,3S)N1-[(3S)-hexahydro-1-(phenyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Step (3a): Triethylamine (1.5 mL, 10.8 mmoles), copper (II) acetate(0.95 g, 5.2 mmoles) and phenylboric acid (1.6 g, 13.1 mmoles) wereadded successively to a solution of compound of Step (1a) (1.0 g, 4.4mmoles) in dichloromethane (20 ml). After 2.5 h at rt, more phenylboricacid (0.5 g, 4.1 mmoles) was added to the mixture. After an additional 3hours at rt more phenylboric acid (0.5 g, 4.1 mmoles) was added to themixture. After 65 h at rt, the mixture was filtered over celite. Thefiltrate was concentrated in vacuo, and the residue was purified bysilica gel chromatography (ethyl acetate:hexanes, 5:95 then 15:85) togive the desired product (250 mg, 19%). MS (M-Ot-Bu)⁺=231.

Step (3b): Following a procedure analogous to the preparation ofcompound of Step (2c), but using compound of Step (3a) (250 mg, 0.82mmoles), the amine (300 mg, 99%) was prepared as a yellow oil. MS(M+H)⁺=205.

Step (3c): Following a procedure analogous to the preparation ofcompound of Step (1e), but using compound from Step (3b) (0.3 g, 0.94mmoles), the amide was prepared. The residue was purified by silica gelchromatography (ethyl acetate:hexanes, 5:95 to 20:80 in 5% increments,500 mL each ratio) to give the desired product (210 mg, 60%) as a clearoil. MS (M+H-t-Bu)⁺=403.

Step (3d): Following a procedure analogous to the preparation ofcompound of Step (1f), but using compound from sStep (3c) (200 mg, 0.44mmoles) the acid was prepared. The crude oil was triturated withether:hexanes 1:1 to give the desired acid (114 mg, 65%) as a whitesolid. MS (M-OH)⁺=385.

Step (3e): Following a procedure analogous to the preparation ofcompound of Step (1g), but using compound from Step (3d) (82 mg, 0.20mmoles) the title compound was prepared. The crude product was purifiedby reverse phase HPLC on a Vydac C-18 column to give the desired product(80 mg, 94%). MS (M-H)=416.

Example 4 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Following a procedure analogous to the preparation of Example 3,compound of Step (2e) (100 mg, 0.20 mmol) was treated with HATU(O-(7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluroniumhexafluorophosphate) (114 mg, 0.30 mmol) and N-methyl morpholine (66 mL,0.6 mmol) in 2 mL of DMF for 15 min at rt. A solution of 2.0 Mmethylamine in THF (0.2 mL, 0.4 mmol) was added and the reactionsolution was stirred for 1 h at rt. The reaction solution was dilutedwith 1N HCl (5 mL) and extracted 3× with 10 mL of ethyl acetate. Thecombined organic layers were washed with a saturated sodium bicarbonatesolution (5 mL) and brine (5 mL), dried over magnesium sulfate, andconcentrated in vacou to provide the crude amide. Purification byreverse phase HPLC on a Vydac-18 column provided the desired amide (30mg, 30%). MS (M+Na)⁺=544.

Example 5 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methoxy)-N-4-(methyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Following a procedure analogous to the preparation of Example 4,compound of Step (2e) (100 mg, 0.20 mmol) was activated and condensedwith N,O-dimethylhydroxylamine hydrochloride (40 mg, 0.40 mmol).Purification by reverse phase HPLC on a Vydac-18 column provided thedesired amide (30 mg, 30%). MS (M+Na)⁺=574.

Example 6 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(methoxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Following a procedure analogous to the preparation of Example 4,compound of Step (2e) (100 mg, 0.20 mmol) was activated and condensedwith O-methylhydroxylamine hydrochloride (40 mg, 0.40 mmol).Purification by reverse phase HPLC on a Vydac-18 column provided thedesired amide (30 mg, 30%). MS (M+Na)⁺=560.

Example 7 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

Following a procedure analogous to the preparation of Example 4,compound of Step (2e) (100 mg, 0.20 mmol) was activated and condensedwith a 2.0 M solution of ammonia in dioxane (0.2 mL, 0.4 mmol).Purification by reverse phase HPLC on a Vydac-18 column provided thedesired amide (30 mg, 30%). MS (M+Na)⁺=530.

Example 7A (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(amino)-2-(2-methylpropyl)-3-(propyl)-butanediamide

Following a procedure analogous to the preparation of Example 4,compound of Step (2e) (100 mg, 0.20 mmol) was activated and condensedwith hydrazine (13 mg, 0.4 mmol). Purification by reverse phase HPLC ona Vydac-18 column provided the desired amide (11.1 mg, 21%). MS(M+Na)⁺=542.

Example 8 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

(8a) Compound 8a was synthesized following a procedure analogous to thepreparation of the compound 1e, but using the caprolactam 2c (2.5 g,5.89 mmol), succinate 9 (1.64 g, 6.0 mmol), and HATU instead of TBTU.The compound was purified by chromatogrphy eluting with 5% methanol inCH₂Cl₂ to afford 1.50 g (45%) of the desired ester.

(8b) The ester from 8a (1.18 g, 2.10 mmol) was dissolved in 10 mL of a50% solution of trifluoroacetic acid in CH₂Cl₂ and stirred at rt for 2h. The solvents were removed by concentration under reduced pressure andthe crude product was dissolved in 10 mL of toluene and reconcentratedtwice to remove residual TFA. The crude acid was used without furtherpurification or characterization.

Following a procedure analogous to the preparation of Example 7,compound 8b (1.065 g, 2.10 mmol) was activated and condensed with anexcess of gaseous ammonia. Purification by reverse phase HPLC on aVydac-18 column provided 500 mg (47%) of the desired compound of Example8. MS (M+Na)⁺=528.

Example 9 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(allyl)-butanediamide

Example 9 was synthesized following a procedure analogous to thepreparation of Example 2, but using succinate 9 (Scheme 2). Purificationby reverse phase HPLC on a Vydac-18 column provided 150 mg of Example 9.MS (M+Na)⁺=544.

Example 10 (2R,3S)N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using2,4-dichlorophenyl boronic acid. Purification afforded 6.0 mg (60%) ofthe desired product. MS (M+Na)⁺=598.

Example 11 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using4-fluorophenyl boronic acid. Purification afforded 5.0 mg (54%) of thedesired product. MS (M+Na)⁺=548.

Example 12 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using4-methylphenyl boronic acid. Purification afforded 3.0 mg (33%) of thedesired product. MS (M+Na)⁺=544.

Example 13 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using4-methoxyphenyl boronic acid. Purification afforded 3.0 mg (32%) of thedesired product. MS (M+Na)⁺=560.

Example 14 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using3-methylphenyl boronic acid. Purification afforded 3.0 mg (33%) of thedesired product. MS (M+Na)⁺=544.

Example 15 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using3-chloro-4-fluorophenyl boronic acid. Purification afforded 4.0 mg (41%)of the desired product. MS (M+Na)⁺=582.

Example 16 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using4-trifluoromethylphenyl boronic acid. Purification afforded 4.0 mg (40%)of the desired product. MS (M+Na)⁺=598.

Example 17 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using3-methoxyphenyl boronic acid. Purification afforded 4.1 mg (44%) of thedesired product. MS (M+Na)⁺=560.

Example 18 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using3-fluorophenyl boronic acid. Purification afforded 3.5 mg (38%) of thedesired product. MS (M+Na)⁺=548.

Example 19 (2R,3S)N1-[(3S)-hexahydro-1-(3-(2-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using2-methoxyphenyl boronic acid. Purification afforded 1.3 mg (14%) of thedesired product. MS (M+Na)⁺=560.

Example 20 (2R,3S)N1-[(3S)-hexahydro-1-(3-(2-naphthyl)benzyl)-2-oxo-1H-azepin-3-yl]-N-4-(hydroxy)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 5 was followed using2-naphthyl boronic acid. Purification afforded 3.0 mg (31%) of thedesired product. MS (M+Na)⁺=580.

It will be understood by one skilled in the art that Scheme 6 can befollowed in a manner analogous to the procedure for Scheme 5.

Example 21 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using4-methoxyphenyl boronic acid. Purification afforded 0.5 mg of thedesired product. MS (M+Na)⁺=544.

Example 22 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using3-fluorophenyl boronic acid. Purification afforded 1.6 mg of the desiredproduct. MS (M+Na)⁺=532.

Example 23 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using4-trifluoromethylphenyl boronic acid. Purification afforded 0.7 mg(4.3%) of the desired product. MS (M+Na)⁺=582.

Example 24 (2R,3S)N1-[(3S)-hexahydro-1-(3-(2,4-dichlorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using2,6-dichlorophenyl boronic acid. Purification afforded 1.8 mg (11%) ofthe desired product. MS (M+Na)⁺=582.

Example 25 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using 4-tolylboronic acid. Purification afforded 1.8 mg (12%) of the desired product.MS (M+Na)⁺=528.

Example 26 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using4-methoxyphenyl boronic acid. Purification afforded 0.5 mg (3.3%) of thedesired product. MS (M+Na)⁺=544.

Example 27 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using4-fluoro-3-chlorophenyl boronic acid. Purification afforded 0.5 mg(3.3%) of the desired product. MS (M+Na)⁺=567.

Example 28 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using2-methoxyphenyl boronic acid. Purification afforded 0.8 mg (5.3%) of thedesired product. MS (M+Na)⁺=544.

Example 29 (2R,3S)N1-[(3S)-hexahydro-1-(3-(2-methoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 6 was followed using2-methoxyphenyl boronic acid. Purification afforded 1.5 mg (10%) of thedesired product. MS (M+Na)⁺=544.

It will be understood by one skilled in the art that Scheme 7 can befollowed in a manner analogous to the procedure for Schemes 5 and 6.

Example 30 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-methoxyphenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

Amide 35 of Scheme 7 (0.10 g, 0.18 mmol) was dissolved in 5 mL oftoluene and 41 mg (0.27 mmol) of 4-methoxyphenyl boronic acid was added,followed by 31 mg (0.0147 mmol) oftetrakis(triphenylphosphine)palladium, 0.5 mL of a 2M odium cabonatesolution and 0.5 mL of methanol. The reaction solution was heated toreflux for 16 h and then allowed to cool to rt. The reaction solutionwas diluted with 10 mL of water and extracted 2× with 50 mL of ethylacetate. The combined organic layers were dried and concentrated and theresulting oil was purified by chromatography eluting with 30 to 100%ethyl acetate in hexanes as a solvent to provide 30 mg (29%) of biarylproduct. MS (M+H)⁺=580.

The purified biaryl product was dissolved in 10 mL of 1:1trifluoroacetic acid/CH₂Cl₂ and stirred at rt for 2 h. The solvents werethen removed under reduced pressure and the resulting oil wasredissolved in 5 mL of toluene and reconcentrated to remove residualTFA. The crude acid (25 mg, 0.047 mmol) was then dissolved in 1 mL ofDMF and 10 mL of N-methylmorpholine (0.094 mmol) and 42 mg (0.062 mmol)HATU were added and the reaction solution was stirred at rt for 45 min.Gaseous ammonia was then bubbled in at a gentle rate for about 1 minuteand the solution was stirred for an additional 1 min. The reactionsolution was then diluted with 10 mL of water and extracted 3× with 30mL of ethyl acetate. The combined organic layers were dried andconcentrated under reduced pressure to a solid which was purified byreversed phase HPLC to provide 3.5 mg (10%) of the compound of Example30 as its trifluoroacetic acid salt. MS (M+H)⁺=523.

Example 31 (2R,3S)N1-[(3S)-hexahydro-1-(3-(4-trifluoromethylphenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for the compound of Example 30 wasfollowed using 4-trifluoromethylphenyl boronic acid. Purification byHPLC afforded 6.0 mg of the desired product from as its trifluoroaceticacid salt. MS (M+Na)⁺=583.

Example 32 (2R,3S)N1-[(3S)-hexahydro-1-(3-(3-chloro-4-fluorophenyl)pyrid-5-ylmethyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

Amide 35 (0.30 g, 0.54 mmol) was dissolved in 3 mL of DMF and 123 mg(0.70 mmol) of 4-methoxyphenyl boronic acid was added, followed by 44 mg(0.0543 mmol) of bis(diphenylphosphinoferrocene)palladim (II) dichlorideand 1.0 mL (7.18 mmol) of triethylamine. The reaction solution washeated to 80° C. for 24 h and then allowed to cool to rt. The reactionsolution was diluted with 10 mL of water and extracted 2× with 50 mL ofethyl acetate. The combined organic layers were dried and concentratedand the resulting oil was purified by chromatography eluting with 20 to100% ethyl acetate in hexanes as a solvent to provide 140 mg (50%) ofbiaryl product. MS (M+Na)⁺=624.

The general procedure reported for the compound of Example 30 was thenfollowed to provide the amide. Purification by chromatography elutingwith 20 to 100% ethyl acetate in hexanes afforded 45 mg of the desiredproduct of Example 32 as its trifluoroacetic acid salt. MS (M+Na)⁺=567.

Example 33 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(butyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 8 was followed usingbutylamine. Analysis by ¹HNMR integration relative to an internalstandard revealed a yield of 100% of the desired product. MS(M+Na)⁺=586.

Example 34 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(2-furylmethyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 8 was followed using2-furylmethylamine. Analysis by ¹HNMR integration relative to aninternal standard revealed a yield of 75% of the desired product. MS(M+Na)⁺=610.

Example 35 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(cyclopentyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 8 was followed usingcyclopentylamine. Analysis by ¹HNMR integration relative to an internalstandard revealed a yield of 42% of the desired product. MS (M+Na)⁺=598.

Example 36 (2R,3S)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-N-4-(cinnamyl)-2-(2-methylpropyl)-3-(propyl)-butanediamide

The general procedure reported for Scheme 8 was followed usingcinnamylamine. Analysis by ¹HNMR integration relative to an internalstandard revealed a yield of 100% of the desired product. MS(M+Na)⁺=646.

Example 37 (2R,3S)N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide

3-Bromomethylbenzophenone. A solution of 3-methylbenzophenone (20 g, 102mmol) dissolved in 40 mL of 1,2-dibromoethane was heated to reflux. Overa period of about 3 hours a solution of 105 mmol of bromine dissolved in6 mL of 1,2-dibromoethane was added to the refluxing solution. After theaddition was complete the solution was allowed to cool to rt and dilutedwith 100 mL of dichloromethane. The organic layer was extracted with1×25 mL of 1 N HCl, 2×15 mL of NaHCO₃ Solution, and 2×25 ML of brine.The organic layers were dried over magnesium sulfate and concentrated invacuo. The residue was then distilled to afford the product, 16.5 g(60%) as an oil that solidified upon standing, b.p. 160° C. at 300mTorr. ¹H NMR analysis shows that the product contains approximately 7%of the dibromide.

3-(1,1-dimethylethylcarbmethoxy-N-(benzophenone-3-yl-methyl)caprolactam.Diisopropylamine (4.2 mL, 30 mmol) was dissolved in 25 mL of THF andchilled to −78° C. To the solution was added 10 mL of 2.5Mn-butyllithium in hexanes and the solution was warmed to 0° C. andallowed to stir for 10 min. A solution of Boc-protected aminocaprolactam1a (5.0 grams, 22 mmol) dissolved in 25 mL of THF was then added and thereaction solution was stirred for 1 h at 0° C. Solid3-bromomethyl-benzophenone was then added and the reaction solution wasallowed to warm to rt and stir overnight. The reaction solution wasdiluted with water and extracted into ethyl acetate (100 mL). Theorganic layer was rinsed with 2×25 mL of 1 N HCl, 2×25 mL of saturatedNaHCO₃ and 2×25 mL of brine, dried over magnesium sulfate, and dried invacuo. Chromatography eluting with a gradient of 30% to 40% ethylacetate in hexanes afforded the pure benzophenone-substitutedcaprolactam derivative (7.4 g, 80%). MS (M+Na)⁺=445.

The compound of Example 10 was synthesized in a manner analagous to thesynthesis of the compound of Example 8 using succinate 9 and thebenzophenone-substituted caprolactam derivative. The compound waspurified by crystallization from ethyl acetate to afford 0.26 g ofcrystals. MS (M+Na)⁺=540.

Example 38 (2R,3S)N1-[(3S)-hexahydro-1-(benzophenon-3-yl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

The compound of Example 11 was synthesized in a manner analagous to thesynthesis of the compound of Example 8 using succinate 10 and thebenzophenone-substituted caprolactam derivative. The compound waspurified by crystallization from ethyl acetate to afford 0.25 g ofcrystals. MS (M+Na)⁺=542.

Example 39 (2R,3S)N1-[(3S)-hexahydro-1-(4-(4-trifluoromethylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(propyl)-butanediamide

(39-a)3-(1,1-dimethylethylcarbomethoxy-N-(4-bromophenylmethyl)caprolactam. Thetitle compound was synthesized in a manner analogous to the preparationof3-(1,1-dimethylethylcarbomethoxy-N-(benzophenone-3-yl-methyl)caprolactamin Example 10 but using 4-bromobenzyl bromide as the alkylaing agent.The compound was purified by chromatography eluting with 5-20% ethylacetate in hexanes as eluent to provide 7.0 g (70%) of the titlecompound as a solid. MS (M+Na)⁺=419.

(39-b)3-(1,1-dimethylethylcarbomethoxy-N-(4,-(4′-trifluoromethylphenyl)phenylmethyl)caprolactam.To a solution of3-(1,1-dimethylethylcarbomethoxy-N-(4-bromophenylmethyl)caprolactam (0.5g, 1.26 mmol) dissolved in 10 mL of toluene was added 263 mg (1.38 mmol)of 4-trifluoromethylphenyl boronic acid, 1 mL of methanol, and 1 mL of a2M solution of potassium carbonate. The solution was degassed bynitrogen bubbling for 5 min, and then 33 mg oftris(dibenzylideneacetone)dipalladium (0) chloroform adduct and 66 mg oftriphenylphosphine was added. The solution ws heated to reflux for 16 hand then allowed to cool and diluted with 20 mL of water. The aqueouslayer was extracted 3× with 25 mL of ethyla acetate and concentrated.The resulting oil was purified by chromatography eluting with 20% ethylacetate in hexanes to afford 0.47 g (81%) of an oil which crystallizedon standing.

(39-d) The compound 39-d was synthesized in a manner analagous to thesynthesis of the compound of Example 8 using succinate 10 (280 mg, 1.04mmol) and3-(1,1-dimethylethylcarbomethoxy-N-(4,-(4′-trifluoromethylphenyl)-phenylmethyl)caprolactam.The compound was purified by chromatography eluting with 20-100% ethylacetate in hexanes to afford 40 mg of a white powder. MS (M+H)⁺=560.

Example 40 (2S,3R)N1-[(3S)-hexahydro-1-(3-(2-tetrazolylphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(propyl)-3-(2-methylpropyl)-butanediamide

(40-a) The compound of Example 40 was synthesized in a manner analogousto the synthesis of the compound of Example 39, but using thesubstituted acid 28 of Scheme 6 (50 mg, 0.10 mmol) ando-((N-trityl)-tetrazole)phenylboronic acid under the conditions for theformation of the compound (39-b). The desired biaryl acid was isolatedas an impure mixture (134 mg) and used directly in the next step.

(40-b) The acid 40-a (134 mg, impure mixture) was converted to the amideunder the conditions reported for the compound of Example 8. The crudeamide was then dissolved in 2 mL of 10% trifluoroacetic acid in methanoland allowed to stir at rt for 30 min. The solvents were removed and theresidue was purified by chromatography eluting with 10% methanol inethyl acetate to provide 40 mg (71%, 2 steps) of the compound of Example40 as a sticky powder. MS (M+Na)⁺=582.

Example 41 (2S,3R)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(propyl)-3-(2-methylpropyl)-butanediamide

(41-a) The compound of Example 41 is formed by coupling Succinate 23(480 mg, 1.21 mmol) with the substituted caprolactam TFA salt 2c underthe conditions reported for the synthesis of the compound of Example 8.The crude fluorenylmethyl ester was used in the next step with outfurther purification. MS (M+Na)+=709.

(41-b) The crude fluorenylmethyl ester is dissolved in 2 mL of a 50%solution of piperidine in CH₂Cl₂ and stirred for 3 h at rt. A 10 mLportion of 1N HCl was then added and the mixture was extracted 3× with10 mL of ethyl acetate. The crude acid was used in the next step without further purification. MS (M+H)+=509.

The compound of Example 41 was then prepared using the acid 41-b underthe conditions reported for compound of Example 28. The compound waspurified by chromatography eluting with 5% methanol in CH₂Cl₂ to afford120 mg (19%, 3 steps) of a white powder. MS (M+H)+=508.

Example 42 (2S,3R)N1-[1,3-dihydro-1-(3-phenoxybenzyl)-2-oxo-5-(phenyl)-2H-1,4-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamide

3-Phenoxybenzyl iodide: To a solution of 3-phenoxybenzyl chloride (10.0g, 45.7 mmol) in 200 ml acetone was added sodium iodide (7.6 g, 507mmol). The mixture was stirred at temperature overnight. The mixture wasdiluted with 300 ml hexane and the organic layer was washed twice with5% sodium bicarbonate, once with brine and then dried over MgSO₄.Evaporation of the filtrate gave a light yellow oil. The product wasused in next step without purification. ¹H NMR (CDCl₃) 4.4 (s,2H),6.8-7.4 (m, 9H).

Synthesis of Example 42:

To a solution of benzodiazepine 50 (910 mg, 3.63 mmol), succinate 2 (980mg, 3.63 mmol), hydroxybenzotriazole (980 mg., 7.25 mmol) and EDC (870mg, 4.54 mmol) in 100 ml CH₂Cl₂ at 0 degrees was added triethylamine(0.76 ml, 5.45 mmol). The reaction mixture was washed with saturatedsodium bicarbonate solution, 1.0N HCl, brine and dried over MgSO₄.Evaporation of the organic layer and purification by columnchromatography on silica gel with hexane-ethyl acetate (7:3) gave 610 mgof benzodiazepine 51 as a white solid. M+H=504.37. ¹H NMR (CDCl₃)0.8-1.0 (m, 6H), 1.0-1.2 (m, 1H), 1.4-1.5 (d, 9H), 1.6-1.9 (m, 2H),2.2-2.8 (m, 4H), 4.9-5.2 (m, 2H), 5.6 (dd, 1H), 5.6-6.0 (m, 1H), 7.0-7.6(m, 9H).

To a solution of benzodiazepine 5 (440 mg, 0.875 mmol) in DMF (20 ml) at0 degrees was added NaH (45 mg, 1.12 mmol). The mixture was stirred at 0degrees for 1.5 hr and then a solution of 3-phenoxylbenzyl iodide (330mg, 1.06 mmol) in 10 ml DMF was added dropwise. The reaction mixture wasallowed to warm to room temperature and stirred overnight. TLC usinghexanes:EtOAc 6:4 (product Rf=0.31) indicated that the reaction wascomplete. The reaction mixture was quenched with water, and the solventwas evaporated under high vacuum, which provided a viscous yellow oil.The product benzodiazepine 52 was dissolved in ethyl acetate, which waswashed with water (2×), brine and then dried over MgSO₄.

Evaporation of solvent gave 600 mg of benzodiazepine 52 as a yellow oilwhich was not further purified. M+H=686.3, M+Na=708.3. ¹H NMR (CDCl₃)0.8-1.0 (m, 6H), 1.0-1.3 (m, 1H), 1.4-1.5 (d, 9H), 1.5-1.9 (2H), 2.2-2.7(4H), 4.6-4.8 (d,1H), 4.9-5.2 (m, 2H), 5.6-5.9 (m, 3H), 6.6-7.6 (m,18H).

A solution of benzodiazepine 52 in 40 ml of TFA/CH₂Cl₂ (1:1) was stirredovernight at room temperature then evaporated to dryness. Repeatedaddition of toluene and evaporation provided 560 mg. of 53 as a yellowsolid. (M−H=629.1)

To a solution of benzodiazepine 53 and HATU (410 mg, 1.08 mmol) in 30 mlDMF was added diisopropylethylamine (0.6 ml, 3.44 mmol) at 0 degrees.After 10 minutes, ammonia gas was bubbled through the solution for twominutes, and the reaction mixture was allowed to warm to roomtemperature and stirred overnight. Addition of water and solventevaporation under high vacuum provided a yellow solid. The solid wastaken up in ethyl acetate-water (1:1), and the organic layer was washedwith water (2×), brine and then dried over MgSO₄. Evaporation of solventgave a light yellow solid. Chromatographic purification on silica gelusing CH₂Cl₂:methanol (10:0.5) gave 256 mg of Example 42. M+H=629.2 HNMR(CDCl₃) 0.8-1.0 (m, 6H), 1.2-1.4 (m, 1H), 1.6-2.0 (m, 2H), 2.2-2.8(4H),4.6-4.8 (m, 1H), 5.0-5.2(m, 2H), 5.6-5.9 (m, 3H), 6.2-7.8 (m, 18H).

Example 43 (2R)N1-[(3S)-hexahydro-1-(3-phenoxybenzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-butanediamide

Step (43a): The compound of Step (43a) is formed by coupling succinate 7(115 mg, 0.5 mmol) with the substituted caprolactam TFA salt (212 mg,0.5 mmol) from Step (2c) of Example 2 under the conditions reported forthe synthesis of the compound of Example 8. The crude tert-butyl esterwas taken on without further purification.

Step (43b): The compound of Step (43b) is formed by dissolving the crudeproduct from Step (43a) in 5 mL of a 1:1 solution of TFA/CH₂Cl₂ andstirring at room temperature for 2 hours. Concentration followed byreconcentration twice from 10 mL of toluene provides the crude acidwhich was taken on with no further purification.

Step (43c): The title compound, Example 43, was prepared using the acidfrom Step (43b) under the conditions reported for the compound ofExample 7. The compound was purified by chromatography eluting with 5%methanol in CH₂Cl₂ to afford 50 mg (21%, 3 steps) of a white powder. MS(M+Na)⁺=488.

Utility

Aβ production has been implicated in the pathology of Alzheimer'sDisease (AD). The compounds of the present invention have utility forthe prevention and treatment of AD by inhibiting Aβ production. Methodsof treatment target formation of Aβ production through the enzymesinvolved in the proteolytic processing of β-amyloid precursor protein.Compounds that inhibit b or g secretase activity, either directly orindirectly, control the production of Aβ. Such inhibition of β or γsecretases reduces production of Aβ, and is expected to reduce orprevent the neurological disorders associated with Aβ protein, such asAlzheimer's Disease.

Cellular screening methods for inhibitors of Aβ production, testingmethods for the in vivo suppression of Aβ production, and assays for thedetection of secretase activity are known in the art and have beendisclosed in numerous publications, including PCT publication number WO98/22493, EPO publication number 0652009, U.S. Pat. No. 5,703,129 andU.S. Pat. No. 5,593,846; all hereby incorporated by reference.

The compounds of the present invention have utility for the preventionand treatment of disorders involving Aβ production, such ascerebrovascular disorders.

Compounds of the present invention have been shown to inhibit Aβproduction, as determined by the secretase inhibition assay describedbelow.

Compounds of the present invention have been shown to inhibit Aβproduction, utilizing the C-terminus b amyloid precursor proteinaccumulation assay described below.

Compounds of Formula (I) are expected to possess γ-secretase inhibitoryactivity. The γ-secretase inhibitory activity of the compounds of thepresent invention is demonstrated using assays for such activity, forExample, using the assay described below. Compounds of the presentinvention have been shown to inhibit the activity of γ-secretase, asdetermined by the Aβ immunoprecipitation assay.

Compounds provided by this invention should also be useful as standardsand reagents in determining the ability of a potential pharmaceutical toinhibit Aβ production. These would be provided in commercial kitscomprising a compound of this invention.

As used herein “μg” denotes microgram, “mg” denotes milligram, “g”denotes gram, “μL” denotes microliter, “mL” denotes milliliter, “L”denotes liter, “nM” denotes nanomolar, “μM” denotes micromolar, “mM”denotes millimolar, “M” denotes molar, “nm” denotes nanometer, “SDS”denotes sodium dodecyl sulfate, and “DMSO” denotes dimethyl sulfoxide,and “EDTA” denotes ethylenediaminetetraacetato.

A compound is considered to be active if it has an IC₅₀ or K_(i) valueof less than about 100 μM for the inhibition of Aβ production orinhibition of proteolytic activity leading to Aβ production. Compounds,as demonstrated by use of the invention, have demonstrated IC₅₀ values,for the inhibition of Aβ production, of less than about 100 μM.Preferably compounds, as demonstrated by use of the invention,demonstrate IC₅₀ values, for the inhibition of Aβ production, of lessthan about 1 μM. More preferably compounds, as demonstrated by use ofthe invention, demonstrate IC₅₀ values, for the inhibition of Aβproduction, of less than about 100 nM. Even more preferably compounds,as demonstrated by use of the invention, demonstrate IC₅₀ values, forthe inhibition of Aβ production, of less than about 50 nM.

β Amyloid Precursor Protein Accumulation Assay (βAPPA Assay)

An assay to evaluate the accumulation of Aβ protein was developed todetect potential inhibitors of secretases. The assay uses the N 9 cellline, characterized for expression of exogenous APP by immunoblottingand immunoprecipitation.

The effect of test compounds on the accumulation of Aβ in theconditioned medium is tested by immunoprecipitation. N 9 cells are grownto confluency in 6-well plates and washed twice with 1×Hank's bufferedsalt solution. The cells are starved in methionine/cysteine deficientmedia for 30 min., followed by replacement with fresh deficient mediacontaining 150 uCi Tran35S-LABEL™ (ICN). Test compounds dissolved inDMSO (final concentration 1%) are added, over a range of 1 picomolar to100 micromolar, together with the addition of the fresh media containingTran35S-LABEL™. The cells are incubated for 4 h at 37° C. in a tissueculture incubator.

At the end of the incubation period, the conditioned medium is harvestedand pre-cleared by the addition of 5 μl normal mouse serum and 50 ul ofprotein A Sepharose (Pharmacia), mixed by end-over-end rotation for 30minutes at 4° C., followed by a brief centrifugation in a microfuge. Thesupernatant is then harvested and transferred to fresh tubes containing5 ug of a monoclonal antibody (examples of antibodies include but arenot limited by, clone 1101.1, directed against an internal peptidesequence in Aβ; or 6E10 from Senetek; or 4G8 from Senetek; additionallypolyclonals from rabbit antihuman Aβ from Boehringer Mannheim) and 50 μlprotein A Sepharose. After incubation overnight at 4° C., the samplesare washed three times with high salt washing buffer (50 mM Tris, pH7.5, 500 mM NaCl, 5 mM EDTA, 0.5% Nonidet P-40), three times with lowsalt wash buffer (50 mM Tris, pH 7.5, 150 mM NaCl, 5 mM EDTA, 0.5%Nonidet P-40), and three times with 10 mM Tris, pH 7.5. The pellet afterthe last wash is resuspended in SDS sample buffer (Laemmli U. K.Cleavage of structural proteins during the assembly of the head ofbacteriphage T4. Nature 227, 680-5, 1970.) and boiled for 3 minutes. Thesupernatant is then fractionated on either 10-20% Tris/Tricine SDS gelsor on 16.5% Tris/Tricine SDS gels. The gels are dried and exposed toX-ray film or analyzed by phosphorimaging. The resulting image isanalyzed for the presence of Aβ polypeptides. The steady-state level ofAβ in the presence of a test compound is compared to wells treated withDMSO (1%) alone. A typical test compound in this assay blocks Aβaccumulation in the conditioned medium, and is considered active with anIC₅₀ less than 100 μM.

C-Terminus β-Amyloid Precursor Protein Accumulation Assay (CTF Assay)

The effect of test compounds on the accumulation of C-terminal fragmentsis determined by immunoprecipitation of APP and fragments thereof fromcell lysates. N 9 cells are metabolically labeled, as above, with mediacontaining Tran35S-LABEL™, in the presence or absence of test compounds.At the end of the incubation period, the conditioned medium areharvested and cells lysed in RIPA buffer (10 mM Tris, pH 8.0 containing1% Triton X-100, 1% deoxycholate, 0.1% SDS, 150 mM NaCl, 0.125% NaN₃).Again, lysates are precleared with 5 ul normal rabbit serum/50 ulprotein A Sepharose, followed by the addition of BC-1 antiserum (15 μl;)and 501 μl protein A Sepharose for 16 hours at 4° C. Theimmunoprecipitates are washed as above, bound proteins eluted by boilingin SDS sample buffer and fractionated by Tris/Tricine SDS-PAGE. Afterexposure to X-ray film or phosphorimager, the resulting images areanalyzed for the presence of C-terminal APP fragments. The steady-statelevel of C-terminal APP fragments is compared to wells treated with DMSO(1%) alone. A typical test compound in this assay stimulates C-terminalfragment accumulation in the cell lysates, and is considered active withan IC₅₀ less than 100 μM.

Accumulation-Release Assay

This immunoprecipitation assay is specific for g secretase activity(i.e., proteolytic activity required to generate the C-terminal end ofAβ either by direct cleavage or generating a C-terminal extended specieswhich is subsequently further proteolyzed). N 9 cells are pulse labeledwith media containing Tran35S-LABEL™ in the presence of a reported gsecretase inhibitor (MDL 28170; Higaki J, Quon D, Zhong Z, Cordell B.Inhibition of beta-amyloid formation identifies proteolytic precursorsand subcellular site of catabolism. Neuron 14, 651-659, 1995) for 1 h,followed by washing to remove ³⁵S radiolabel and MDL 28170. The media isreplaced and test compounds are added over a dose range (for example 0.1nM to 100 uM). The cells are chased for increasing periods of times andAβ is isolated from the conditioned medium and C-terminal fragments fromcell lysates (see accumulation assay above). The activity of testcompounds are characterized by whether a stabilization of C-terminalfragments is observed and whether Aβ is generated from these accumulatedprecursor. A typical test compound in this assay prevents the generationof Aβ out of accumulated C-terminal fragments and is considered activewith an IC₅₀ less than 100 μM.

Dosage and Formulation

The compounds determined from the present invention can be administeredorally using any pharmaceutically acceptable dosage form known in theart for such administration. The active ingredient can be supplied insolid dosage forms such as dry powders, granules, tablets or capsules,or in liquid dosage forms, such as syrups or aqueous suspensions. Theactive ingredient can be administered alone, but is generallyadministered with a pharmaceutical carrier. A valuable treatise withrespect to pharmaceutical dosage forms is Remington's PharmaceuticalSciences, Mack Publishing.

The compounds determined from the present invention can be administeredin such oral dosage forms as tablets, capsules (each of which includessustained release or timed release formulations), pills, powders,granules, elixirs, tinctures, suspensions, syrups, and emulsions.Likewise, they may also be administered in intravenous (bolus orinfusion), intraperitoneal, subcutaneous, or intramuscular form, allusing dosage forms well known to those of ordinary skill in thepharmaceutical arts. An effective but non-toxic amount of the compounddesired can be employed to prevent or treat neurological disordersrelated to β-amyloid production or accumulation, such as Alzheimer'sdisease and Down's Syndrome.

The compounds of this invention can be administered by any means thatproduces contact of the active agent with the agent's site of action inthe body of a host, such as a human or a mammal. They can beadministered by any conventional means available for use in conjunctionwith pharmaceuticals, either as individual therapeutic agents or in acombination of therapeutic agents. They can be administered alone, butgenerally administered with a pharmaceutical carrier selected on thebasis of the chosen route of administration and standard pharmaceuticalpractice.

The dosage regimen for the compounds determined from the presentinvention will, of course, vary depending upon known factors, such asthe pharmacodynamic characteristics of the particular agent and its modeand route of administration; the species, age, sex, health, medicalcondition, and weight of the recipient; the nature and extent of thesymptoms; the kind of concurrent treatment; the frequency of treatment;the route of administration, the renal and hepatic function of thepatient, and the effect desired. An ordinarily skilled physician orveterinarian can readily determine and prescribe the effective amount ofthe drug required to prevent, counter, or arrest the progress of thecondition.

Advantageously, compounds determined from the present invention may beadministered in a single daily dose, or the total daily dosage may beadministered in divided doses of two, three, or four times daily.

The compounds identified using the present invention can be administeredin intranasal form via topical use of suitable intranasal vehicles, orvia transdermal routes, using those forms of transdermal skin patcheswall known to those of ordinary skill in that art. To be administered inthe form of a transdermal delivery system, the dosage administrationwill, of course, be continuous rather than intermittent throughout thedosage regimen.

In the methods of the present invention, the compounds herein describedin detail can form the active ingredient, and are typically administeredin admixture with suitable pharmaceutical diluents, excipients, orcarriers (collectively referred to herein as carrier materials) suitablyselected with respect to the intended form of administration, that is,oral tablets, capsules, elixirs, syrups and the like, and consistentwith conventional pharmaceutical practices.

For instance, for oral administration in the form of a tablet orcapsule, the active drug component can be combined with an oral,non-toxic, pharmaceutically acceptable, inert carrier such as lactose,starch, sucrose, glucose, methyl callulose, magnesium stearate,dicalcium phosphate, calcium sulfate, mannitol, sorbitol and the like;for oral administration in liquid form, the oral drug components can becombined with any oral, non-toxic, pharmaceutically acceptable inertcarrier such as ethanol, glycerol, water, and the like. Moreover, whendesired or necessary, suitable binders, lubricants, disintegratingagents, and coloring agents can also be incorporated into the mixture.Suitable binders include starch, gelatin, natural sugars such as glucoseor β-lactose, corn sweeteners, natural and synthetic gums such asacacia, tragacanth, or sodium alginate, carboxymethylcellulose,polyethylene glycol, waxes, and the like. Lubricants used in thesedosage forms include sodium oleate, sodium stearate, magnesium stearate,sodium benzoate, sodium acetate, sodium chloride, and the like.Disintegrators include, without limitation, starch, methyl cellulose,agar, bentonite, xanthan gum, and the like.

The compounds determined from the present invention can also beadministered in the form of liposome delivery systems, such as smallunilamellar vesicles, large unilamallar vesicles, and multilamellarvesicles. Liposomes can be formed from a variety of phospholipids, suchas cholesterol, stearylamine, or phosphatidylcholines.

Compounds of the present invention may also be coupled with solublepolymers as targetable drug carriers. Such polymers can includepolyvinylpyrrolidone, pyran copolymer,polyhydroxypropylmethacrylamide-phenol,polyhydroxyethylaspartamidephenol, or polyethyleneoxide-polylysinesubstituted with palmitoyl residues. Furthermore, the compoundsdetermined from the present invention may be coupled to a class ofbiodegradable polymers useful in achieving controlled release of a drug,for example, polylactic acid, polyglycolic acid, copolymers ofpolylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxybutyric acid, polyorthoesters, polyacetals, polydihydropyrans,polycyanoacylates, and crosslinked or amphipathic block copolymers ofhydrogels.

Gelatin capsules may contain the active ingredient and powderedcarriers, such as lactose, starch, cellulose derivatives, magnesiumstearate, stearic acid, and the like. Similar diluents can be used tomake compressed tablets. Both tablets and capsules can be manufacturedas sustained release products to provide for continuous release ofmedication over a period of hours. Compressed tablets can be sugarcoated or film coated to mask any unpleasant taste and protect thetablet from the atmosphere, or enteric coated for selectivedisintegration in the gastrointestinal tract.

Liquid dosage forms for oral administration can contain coloring andflavoring to increase patient acceptance. In general, water, a suitableoil, saline, aqueous dextrose (glucose), and related sugar solutions andglycols such as propylene glycol or polyethylene glycols are suitablecarriers for parenteral solutions. Solutions for parenteraladministration preferably contain a water soluble salt of the activeingredient, suitable stabilizing agents, and if necessary, buffersubstances. Antioxidizing agents such as sodium bisulfite, sodiumsulfite, or ascorbic acid, either alone or combined, are suitablestabilizing agents. Also used are citric acid and its salts and sodiumEDTA. In addition, parenteral solutions can contain preservatives, suchas benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol.

Suitable pharmaceutical carriers are described in Remington'sPharmaceutical Sciences, Mack Publishing Company, a standard referencetext in this field.

The Tables below provide representative Examples of compounds of Formula(I) of the present invention. TABLE 3

Ex # R¹ R² R³ Z—Y—X—W  1 H OH propyl 3,3-diphenylpropyl  2 H OH propyl3-phenoxybenzyl  3 H OH propyl phenyl  4 H CH₃ propyl 3-phenoxybenzyl  5CH₃ OCH₃ propyl 3-phenoxybenzyl  6 H OCH₃ propyl 3-phenoxybenzyl  7 H Hpropyl 3-phenoxybenzyl   7A H NH₂ propyl 3-phenoxybenzyl  8 H H allyl3-phenoxybenzyl  9 H OH allyl 3-phenoxybenzyl 10 H OH propyl3-(2,4-dichlorophenyl)- benzyl 11 H OH propyl 3-(4-fluorophenyl)-benzyl12 H OH propyl 3-(4-methylphenyl)-benzyl 13 H OH propyl3-(4-methoxyphenyl)-benzyl 14 H OH propyl 3-(3-methylphenyl)-benzyl 15 HOH propyl 3-(3-chloro-4- fluorophenyl)-benzyl 16 H OH propyl3-(4-trifluoromethyl- phenyl)benzyl 17 H OH propyl3-(3-methophenyl)-benzyl 18 H OH propyl 3-(3-fluorophenyl)-benzyl 19 HOH propyl 3-(2-methophenyl)-benzyl 20 H OH propyl 3-(2-naphthyl)benzyl21 H H propyl 3-(4-methoxyphenyl)-benzyl 22 H H propyl3-(3-fluorophenyl)-benzyl 23 H H propyl 3-(4-F₃C-phenyl)benzyl 24 H Hpropyl 3-(2,4-Cl₂-phenyl)benzyl 25 H H propyl 3-(4-H₃C-phenyl)benzyl 26H H propyl 3-(4-H₃CO-phenyl)benzyl 27 H H propyl3-(3-Cl,4-F-phenyl)benzyl 28 H H propyl 3-(3-H₃CO-phenyl)benzyl 29 H Hpropyl 3-(2-H₃CO-phenyl)benzyl 30 H H propyl 3-(4-H₃CO-phenyl)-pyrid-5-ylmethyl 31 H H propyl 3-(4-F₃C-phenyl)-pyrid-5- ylmethyl 32 H H propyl3-(3-Cl,4-F-phenyl)-pyrid- 5-ylmethyl 33 H n-butyl propyl3-phenoxybenzyl 34 H 2-furyl- propyl 3-phenoxybenzyl methyl 35 H C₅H₉propyl 3-phenoxybenzyl 36 H cinnamyl propyl 3-phenoxybenzyl 37 H H allylbenzophenone-3-yl-methyl 38 H H propyl benzophenone-3-yl-methyl 39 H Hpropyl 4-(4-F₃C-phenyl)benzyl  40* H H i-butyl 3-(2-tetrazolyl-phenyl)-R⁵ = propyl benzyl  41* H H i-butyl 3-phenoxybenzyl R⁵ = propyl 43 H H H3-phenoxybenzyl*For these compounds the i-butyl substituent on the carbon adjacent toCR³ in the captioned figure is actually n-propyl.

For these compounds the i-butyl substituent on the carbon adjacent toCR³ in the captioned figure is actually n-propyl.

Table 2 demonstrates representative compounds envisaged within the scopeof the present invention. Each formulae at the start of Table 2 areintended to be paired with each entry in the table which follows.

For example the compound (2R,3S)N1-[(3S)-hexahydro-1-(3-(3,4-dimethoxyphenyl)benzyl)-2-oxo-1H-azepin-3-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamideis represented by Example #139-A-j, which comprises the core A,succinate j, and entry #139.

For example the compound (2R,3S)N1-[6,7-dihydro-5-(3-(3,4-dimethoxyphenyl)benzyl)-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2-(2-methylpropyl)-3-(allyl)-butanediamideis represented by Example #139-B-j, which comprises the core B,succinate j, and entry #139.

For example the compound (2R,3S)N1-[1,3,4,5-tetrahydro-1-(3,4-dimethoxyphenyl)benzyl)-2-oxo-5-(phenyl)-2H-1,5-benzodiazepin-3-yl]-2-(2-methylpropyl)-3-(butyl)-butanediamide,is represented by Example #139-C-ab, which comprises the core C,succinate ab, and entry #139. TABLE 2

A B

C D

E F

G H

J K wherein R³ and R⁵ are:

a b c

d e f

g h i

j k l

m n o

p q r

s t u

v w x

v z aa

ab ac ad

ae af ag

ah ai aj

ak al am

an ao ap

aq ar as

at au av

aw ax ay

az ba bb

bc bd be

bf bg bh

bi bj bk

bl bm bn

bo bp bq

br bs bt Ex # W X Y Z 100 —CH₂— phen-1,3-diyl bond phenyl 101 —CH₂—phen-1,3-diyl bond 3,3-diphenylmethyl 102 —CH₂— phen-1,3-diyl bond2-F-phenyl 103 —CH₂— phen-1,3-diyl bond 3-F-phenyl 104 —CH₂—phen-1,3-diyl bond 4-F-phenyl 105 —CH₂— phen-1,3-diyl bond 2-Cl-phenyl106 —CH₂— phen-1,3-diyl bond 3-Cl-phenyl 107 —CH₂— phen-1,3-diyl bond4-Cl-phenyl 108 —CH₂— phen-1,3-diyl bond 2-Me-phenyl 109 —CH₂—phen-1,3-diyl bond 3-Me-phenyl 110 —CH₂— phen-1,3-diyl bond 4-Me-phenyl111 —CH₂— phen-1,3-diyl bond 2-MeO-phenyl 112 —CH₂— phen-1,3-diyl bond3-MeO-phenyl 113 —CH₂— phen-1,3-diyl bond 4-MeO-phenyl 114 —CH₂—phen-1,3-diyl bond 2-MeS-phenyl 115 —CH₂— phen-1,3-diyl bond3-MeS-phenyl 116 —CH₂— phen-1,3-diyl bond 4-MeS-phenyl 117 —CH₂—phen-1,3-diyl bond 2-F₃C-phenyl 118 —CH₂— phen-1,3-diyl bond3-F₃C-phenyl 119 —CH₂— phen-1,3-diyl bond 4-F₃C-phenyl 120 —CH₂—phen-1,3-diyl bond 2,3-diF-phenyl 121 —CH₂— phen-1,3-diyl bond2,4-diF-phenyl 122 —CH₂— phen-1,3-diyl bond 2,5-diF-phenyl 123 —CH₂—phen-1,3-diyl bond 2,6-diF-phenyl 124 —CH₂— phen-1,3-diyl bond3,4-diF-phenyl 125 —CH₂— phen-1,3-diyl bond 3,5-diF-phenyl 126 —CH₂—phen-1,3-diyl bond 2,3-diCl-phenyl 127 —CH₂— phen-1,3-diyl bond2,4-diCl-phenyl 128 —CH₂— phen-1,3-diyl bond 2,5-diCl-phenyl 129 —CH₂—phen-1,3-diyl bond 2,6-diCl-phenyl 130 —CH₂— phen-1,3-diyl bond3,4-diCl-phenyl 131 —CH₂— phen-1,3-diyl bond 3,5-diCl-phenyl 132 —CH₂—phen-1,3-diyl bond 2-Cl-3-F-phenyl 133 —CH₂— phen-1,3-diyl bond2-Cl-4-F-phenyl 134 —CH₂— phen-1,3-diyl bond 2-Cl-5-F-phenyl 135 —CH₂—phen-1,3-diyl bond 3-Cl-4-F-phenyl 136 —CH₂— phen-1,3-diyl bond3-Cl-5-F-phenyl 137 —CH₂— phen-1,3-diyl bond 4-Cl-2-F-phenyl 138 —CH₂—phen-1,3-diyl bond 4-Cl-3-F-phenyl 139 —CH₂— phen-1,3-diyl bond2,3-diMeO-phenyl 140 —CH₂— phen-1,3-diyl bond 2,4-diMeO-phenyl 141 —CH₂—phen-1,3-diyl bond 2,5-diMeO-phenyl 142 —CH₂— phen-1,3-diyl bond2,6-diMeO-phenyl 143 —CH₂— phen-1,3-diyl bond 3,4-diMeO-phenyl 144 —CH₂—phen-1,3-diyl bond 3,5-diMeO-phenyl 145 —CH₂— phen-1,3-diyl bondcyclopropyl 146 —CH₂— phen-1,3-diyl bond cyclobutyl 147 —CH₂—phen-1,3-diyl bond cyclopentyl 148 —CH₂— phen-1,3-diyl bond cyclohexyl149 —CH₂— phen-1,3-diyl bond 2-furanyl 150 —CH₂— phen-1,3-diyl bond2-thienyl 151 —CH₂— phen-1,3-diyl bond 2-imidazolyl 152 —CH₂—phen-1,3-diyl bond 2-pyridyl 153 —CH₂— phen-1,3-diyl bond 3-pyridyl 154—CH₂— phen-1,3-diyl bond 4-pyridyl 155 —CH₂— phen-1,3-diyl bondN-morpholinyl 156 —CH₂— phen-1,3-diyl bond N-piperidinyl 157 —CH₂—phen-1,3-diyl bond 3-Me-2-pyridyl 158 —CH₂— phen-1,3-diyl bond4-Me-2-pyridyl 159 —CH₂— phen-1,3-diyl bond 1-indolyl 160 —CH₂—phen-1,3-diyl bond 2-benzothienyl 161 —CH₂— phen-1,3-diyl bond2-benzofuranyl 162 —CH₂— phen-1,3-diyl bond 1-benzimidazole 163 —CH₂—phen-1,3-diyl bond 2-naphthyl 164 —CH₂— pyridin-3,5-diyl bond phenyl 165—CH₂— pyridin-3,5-diyl bond 3,3-diphenylmethyl 166 —CH₂—pyridin-3,5-diyl bond 2-F-phenyl 167 —CH₂— pyridin-3,5-diyl bond3-F-phenyl 168 —CH₂— pyridin-3,5-diyl bond 4-F-phenyl 169 —CH₂—pyridin-3,5-diyl bond 2-Cl-phenyl 170 —CH₂— pyridin-3,5-diyl bond3-Cl-phenyl 171 —CH₂— pyridin-3,5-diyl bond 4-Cl-phenyl 172 —CH₂—pyridin-3,5-diyl bond 2-Me-phenyl 173 —CH₂— pyridin-3,5-diyl bond3-Me-phenyl 174 —CH₂— pyridin-3,5-diyl bond 4-Me-phenyl 175 —CH₂—pyridin-3,5-diyl bond 2-MeO-phenyl 176 —CH₂— pyridin-3,5-diyl bond3-MeO-phenyl 177 —CH₂— pyridin-3,5-diyl bond 4-MeO-phenyl 178 —CH₂—pyridin-3,5-diyl bond 2-MeS-phenyl 179 —CH₂— pyridin-3,5-diyl bond3-MeS-phenyl 180 —CH₂— pyridin-3,5-diyl bond 4-MeS-phenyl 181 —CH₂—pyridin-3,5-diyl bond 2-F₃C-phenyl 182 —CH₂— pyridin-3,5-diyl bond3-F₃C-phenyl 183 —CH₂— pyridin-3,5-diyl bond 4-F₃C-phenyl 184 —CH₂—pyridin-3,5-diyl bond 2,3-diF-phenyl 185 —CH₂— pyridin-3,5-diyl bond2,4-diF-phenyl 186 —CH₂— pyridin-3,5-diyl bond 2,5-diF-phenyl 187 —CH₂—pyridin-3,5-diyl bond 2,6-diF-phenyl 188 —CH₂— pyridin-3,5-diyl bond3,4-diF-phenyl 189 —CH₂— pyridin-3,5-diyl bond 3,5-diF-phenyl 190 —CH₂—pyridin-3,5-diyl bond 2,3-diCl-phenyl 191 —CH₂— pyridin-3,5-diyl bond2,4-diCl-phenyl 192 —CH₂— pyridin-3,5-diyl bond 2,5-diCl-phenyl 193—CH₂— pyridin-3,5-diyl bond 2,6-diCl-phenyl 194 —CH₂— pyridin-3,5-diylbond 3,4-diCl-phenyl 195 —CH₂— pyridin-3,5-diyl bond 3,5-diCl-phenyl 196—CH₂— pyridin-3,5-diyl bond 2-Cl-3-F-phenyl 197 —CH₂— pyridin-3,5-diylbond 2-Cl-4-F-phenyl 198 —CH₂— pyridin-3,5-diyl bond 2-Cl-5-F-phenyl 199—CH₂— pyridin-3,5-diyl bond 3-Cl-4-F-phenyl 200 —CH₂— pyridin-3,5-diylbond 3-Cl-5-F-phenyl 201 —CH₂— pyridin-3,5-diyl bond 4-Cl-2-F-phenyl 202—CH₂— pyridin-3,5-diyl bond 4-Cl-3-F-phenyl 203 —CH₂— pyridin-3,5-diylbond 2,3-diMeO-phenyl 204 —CH₂— pyridin-3,5-diyl bond 2,4-diMeO-phenyl205 —CH₂— pyridin-3,5-diyl bond 2,5-diMeO-phenyl 206 —CH₂—pyridin-3,5-diyl bond 2,6-diMeO-phenyl 207 —CH₂— pyridin-3,5-diyl bond3,4-diMeO-phenyl 208 —CH₂— pyridin-3,5-diyl bond 3,5-diMeO-phenyl 209—CH₂— pyridin-3,5-diyl bond cyclopropyl 210 —CH₂— pyridin-3,5-diyl bondcyclobutyl 211 —CH₂— pyridin-3,5-diyl bond cyclopentyl 212 —CH₂—pyridin-3,5-diyl bond cyclohexyl 213 —CH₂— pyridin-3,5-diyl bond2-furanyl 214 —CH₂— pyridin-3,5-diyl bond 2-thienyl 215 —CH₂—pyridin-3,5-diyl bond 2-imidazolyl 216 —CH₂— pyridin-3,5-diyl bond2-pyridyl 217 —CH₂— pyridin-3,5-diyl bond 3-pyridyl 218 —CH₂—pyridin-3,5-diyl bond 4-pyridyl 219 —CH₂— pyridin-3,5-diyl bondN-morpholinyl 220 —CH₂— pyridin-3,5-diyl bond N-piperidinyl 221 —CH₂—pyridin-3,5-diyl bond 3-Me-2-pyridyl 222 —CH₂— pyridin-3,5-diyl bond4-Me-2-pyridyl 223 —CH₂— pyridin-3,5-diyl bond 1-indolyl 224 —CH₂—pyridin-3,5-diyl bond 2-benzothienyl 225 —CH₂— pyridin-3,5-diyl bond2-benzofuranyl 226 —CH₂— pyridin-3,5-diyl bond 1-benzimidazole 227 —CH₂—pyridin-3,5-diyl bond 2-naphthyl 228 —CH₂— pyridin-2,6-diyl bond phenyl229 —CH₂— pyridin-2,6-diyl bond 3,3-diphenylmethyl 230 —CH₂—pyridin-2,6-diyl bond 2-F-phenyl 231 —CH₂— pyridin-2,6-diyl bond3-F-phenyl 232 —CH₂— pyridin-2,6-diyl bond 4-F-phenyl 233 —CH₂—pyridin-2,6-diyl bond 2-Cl-phenyl 234 —CH₂— pyridin-2,6-diyl bond3-Cl-phenyl 235 —CH₂— pyridin-2,6-diyl bond 4-Cl-phenyl 236 —CH₂—pyridin-2,6-diyl bond 2-Me-phenyl 237 —CH₂— pyridin-2,6-diyl bond3-Me-phenyl 238 —CH₂— pyrldin-2,6-diyl bond 4-Me-phenyl 239 —CH₂—pyridin-2,6-diyl bond 2-MeO-phenyl 240 —CH₂— pyridin-2,6-diyl bond3-MeO-phenyl 241 —CH₂— pyridin-2,6-diyl bond 4-MeO-phenyl 242 —CH₂—pyridin-2,6-diyl bond 2-MeS-phenyl 243 —CH₂— pyridin-2,6-diyl bond3-MeS-phenyl 244 —CH₂— pyridin-2,6-diyl bond 4-MeS-phenyl 245 —CH₂—pyridin-2,6-diyl bond 2-F₃C-phenyl 246 —CH₂— pyridin-2,6-diyl bond3-F₃C-phenyl 247 —CH₂— pyridin-2,6-diyl bond 4-F₃C-phenyl 248 —CH₂—pyridin-2,6-diyl bond 2,3-diF-phenyl 249 —CH₂— pyridin-2,6-diyl bond2,4-diF-phenyl 250 —CH₂— pyridin-2,6-diyl bond 2,5-diF-phenyl 251 —CH₂—pyridin-2,6-diyl bond 2,6-diF-phenyl 252 —CH₂— pyridin-2,6-diyl bond3,4-diF-phenyl 253 —CH₂— pyridin-2,6-diyl bond 3,5-diF-phenyl 254 —CH₂—pyridin-2,6-diyl bond 2,3-diCl-phenyl 255 —CH₂— pyridin-2,6-diyl bond2,4-diCl-phenyl 256 —CH₂— pyridin-2,6-diyl bond 2,5-diCl-phenyl 257—CH₂— pyridin-2,6-diyl bond 2,6-diCl-phenyl 258 —CH₂— pyridin-2,6-diylbond 3,4-diCl-phenyl 259 —CH₂— pyridin-2,6-diyl bond 3,5-diCl-phenyl 260—CH₂— pyridin-2,6-diyl bond 2-Cl-3-F-phenyl 261 —CH₂— pyridin-2,6-diylbond 2-Cl-4-F-phenyl 262 —CH₂— pyridin-2,6-diyl bond 2-Cl-5-F-phenyl 263—CH₂— pyridin-2,6-diyl bond 3-Cl-4-F-phenyl 264 —CH₂— pyridin-2,6-diylbond 3-Cl-5-F-phenyl 265 —CH₂— pyridin-2,6-diyl bond 4-Cl-2-F-phenyl 266—CH₂— pyridin-2,6-diyl bond 4-Cl-3-F-phenyl 267 —CH₂— pyridin-2,6-diylbond 2,3-diMeO-phenyl 268 —CH₂— pyridin-2,6-diyl bond 2,4-diMeO-phenyl269 —CH₂— pyridin-2,6-diyl bond 2,5-diMeO-phenyl 270 —CH₂—pyridin-2,6-diyl bond 2,6-diMeO-phenyl 271 —CH₂— pyridin-2,6-diyl bond3,4-diMeO-phenyl 272 —CH₂— pyridin-2,6-diyl bond 3,5-diMeO-phenyl 273—CH₂— pyridin-2,6-diyl bond cyclopropyl 274 —CH₂— pyridin-2,6-diyl bondcyclobutyl 275 —CH₂— pyridin-2,6-diyl bond cyclopentyl 276 —CH₂—pyridin-2,6-diyl bond cyclohexyl 277 —CH₂— pyridin-2,6-diyl bond2-furanyl 278 —CH₂— pyridin-2,6-diyl bond 2-thienyl 279 —CH₂—pyridin-2,6-diyl bond 2-imidazolyl 280 —CH₂— pyridin-2,6-diyl bond2-pyridyl 281 —CH₂— pyridin-2,6-diyl bond 3-pyridyl 282 —CH₂—pyridin-2,6-diyl bond 4-pyridyl 283 —CH₂— pyridin-2,6-diyl bondN-morpholinyl 284 —CH₂— pyridin-2,6-diyl bond N-piperidinyl 285 —CH₂—pyridin-2,6-diyl bond 3-Me-2-pyridyl 286 —CH₂— pyridin-2,6-diyl bond4-Me-2-pyridyl 287 —CH₂— pyridin-2,6-diyl bond 1-indolyl 288 —CH₂—pyridin-2,6-diyl bond 2-benzothienyl 289 —CH₂— pyridin-2,6-diyl bond2-benzofuranyl 290 —CH₂— pyridin-2,6-diyl bond 1-benzimidazole 291 —CH₂—pyridin-2,6-diyl bond 2-naphthyl 292 —CH₂— pyridin-2,4-diyl bond phenyl293 —CH₂— pyridin-2,4-diyl bond 3,3-diphenylmethyl 294 —CH₂—pyridin-2,4-diyl bond 2-F-phenyl 295 —CH₂— pyridin-2,4-diyl bond3-F-phenyl 296 —CH₂— pyridin-2,4-diyl bond 4-F-phenyl 297 —CH₂—pyridin-2,4-diyl bond 2-Cl-phenyl 298 —CH₂— pyridin-2,4-diyl bond3-Cl-phenyl 299 —CH₂— pyridin-2,4-diyl bond 4-Cl-phenyl 300 —CH₂—pyridin-2,4-diyl bond 2-Me-phenyl 301 —CH₂— pyridin-2,4-diyl bond3-Me-phenyl 302 —CH₂— pyridin-2,4-diyl bond 4-Me-phenyl 303 —CH₂—pyridin-2,4-diyl bond 2-MeO-phenyl 304 —CH₂— pyridin-2,4-diyl bond3-MeO-phenyl 305 —CH₂— pyridin-2,4-diyl bond 4-MeO-phenyl 306 —CH₂—pyridin-2,4-diyl bond 2-MeS-phenyl 307 —CH₂— pyridin-2,4-diyl bond3-MeS-phenyl 308 —CH₂— pyridin-2,4-diyl bond 4-MeS-phenyl 309 —CH₂—pyridin-2,4-diyl bond 2-F₃C-phenyl 310 —CH₂— pyridin-2,4-diyl bond3-F₃C-phenyl 311 —CH₂— pyridin-2,4-diyl bond 4-F₃C-phenyl 312 —CH₂—pyridin-2,4-diyl bond 2,3-diF-phenyl 313 —CH₂— pyridin-2,4-diyl bond2,4-diF-phenyl 314 —CH₂— pyridin-2,4-diyl bond 2,5-diF-phenyl 315 —CH₂—pyridin-2,4-diyl bond 2,6-diF-phenyl 316 —CH₂— pyridin-2,4-diyl bond3,4-diF-phenyl 317 —CH₂— pyridin-2,4-diyl bond 3,5-diF-phenyl 318 —CH₂—pyridin-2,4-diyl bond 2,3-diCl-phenyl 319 —CH₂— pyridin-2,4-diyl bond2,4-diCl-phenyl 320 —CH₂— pyridin-2,4-diyl bond 2,5-diCl-phenyl 321—CH₂— pyridin-2,4-diyl bond 2,6-diCl-phenyl 322 —CH₂— pyridin-2,4-diylbond 3,4-diCl-phenyl 323 —CH₂— pyridin-2,4-diyl bond 3,5-diCl-phenyl 324—CH₂— pyridin-2,4-diyl bond 2-Cl-3-F-phenyl 325 —CH₂— pyridin-2,4-diylbond 2-Cl-4-F-phenyl 326 —CH₂— pyridin-2,4-diyl bond 2-Cl-5-F-phenyl 327—CH₂— pyridin-2,4-diyl bond 3-Cl-4-F-phenyl 328 —CH₂— pyridin-2,4-diylbond 3-Cl-5-F-phenyl 329 —CH₂— pyridin-2,4-diyl bond 4-Cl-2-F-phenyl 330—CH₂— pyridin-2,4-diyl bond 4-Cl-3-F-phenyl 331 —CH₂— pyridin-2,4-diylbond 2,3-diMeO-phenyl 332 —CH₂— pyridin-2,4-diyl bond 2,4-diMeO-phenyl333 —CH₂— pyridin-2,4-diyl bond 2,5-diMeO-phenyl 334 —CH₂—pyridin-2,4-diyl bond 2,6-diMeO-phenyl 335 —CH₂— pyridin-2,4-diyl bond3,4-diMeO-phenyl 336 —CH₂— pyridin-2,4-diyl bond 3,5-diMeO-phenyl 337—CH₂— pyridin-2,4-diyl bond cyclopropyl 338 —CH₂— pyridin-2,4-diyl bondcyclobutyl 339 —CH₂— pyridin-2,4-diyl bond cyclopentyl 340 —CH₂—pyridin-2,4-diyl bond cyclohexyl 341 —CH₂— pyridin-2,4-diyl bond2-furanyl 342 —CH₂— pyridin-2,4-diyl bond 2-thienyl 343 —CH₂—pyridin-2,4-diyl bond 2-imidazolyl 344 —CH₂— pyridin-2,4-diyl bond2-pyridyl 345 —CH₂— pyridin-2,4-diyl bond 3-pyridyl 346 —CH₂—pyridin-2,4-diyl bond 4-pyridyl 347 —CH₂— pyridin-2,4-diyl bondN-morpholinyl 348 —CH₂— pyridin-2,4-diyl bond N-piperidinyl 349 —CH₂—pyridin-2,4-diyl bond 3-Me-2-pyridyl 350 —CH₂— pyridin-2,4-diyl bond4-Me-2-pyridyl 351 —CH₂— pyridin-2,4-diyl bond 1-indolyl 352 —CH₂—pyridin-2,4-diyl bond 2-benzothienyl 353 —CH₂— pyridin-2,4-diyl bond2-benzofuranyl 354 —CH₂— pyridin-2,4-diyl bond 1-benzimidazole 355 —CH₂—pyridin-2,4-diyl bond 2-naphthyl 356 —CH₂— pyridin-4,2-diyl bond phenyl357 —CH₂— pyridin-4,2-diyl bond 3,3-diphenylmethyl 358 —CH₂—pyridin-4,2-diyl bond 2-F-phenyl 359 —CH₂— pyridin-4,2-diyl bond3-F-phenyl 360 —CH₂— pyridin-4,2-diyl bond 4-F-phenyl 361 —CH₂—pyridin-4,2-diyl bond 2-Cl-phenyl 362 —CH₂— pyridin-4,2-diyl bond3-Cl-phenyl 363 —CH₂— pyridin-4,2-diyl bond 4-Cl-phenyl 364 —CH₂—pyridin-4,2-diyl bond 2-Me-phenyl 365 —CH₂— pyridin-4,2-diyl bond3-Me-phenyl 366 —CH₂— pyridin-4,2-diyl bond 4-Me-phenyl 367 —CH₂—pyridin-4,2-diyl bond 2-MeO-phenyl 368 —CH₂— pyridin-4,2-diyl bond3-MeO-phenyl 369 —CH₂— pyridin-4,2-diyl bond 4-MeO-phenyl 370 —CH₂—pyridin-4,2-diyl bond 2-MeS-phenyl 371 —CH₂— pyridin-4,2-diyl bond3-MeS-phenyl 372 —CH₂— pyridin-4,2-diyl bond 4-MeS-phenyl 373 —CH₂—pyridin-4,2-diyl bond 2-F₃C-phenyl 374 —CH₂— pyridin-4,2-diyl bond3-F₃C-phenyl 375 —CH₂— pyridin-4,2-diyl bond 4-F₃C-phenyl 376 —CH₂—pyridin-4,2-diyl bond 2,3-diF-phenyl 377 —CH₂— pyridin-4,2-diyl bond2,4-diF-phenyl 378 —CH₂— pyridin-4,2-diyl bond 2,5-diF-phenyl 379 —CH₂—pyridin-4,2-diyl bond 2,6-diF-phenyl 380 —CH₂— pyridin-4,2-diyl bond3,4-diF-phenyl 381 —CH₂— pyridin-4,2-diyl bond 3,5-diF-phenyl 382 —CH₂—pyridin-4,2-diyl bond 2,3-diCl-phenyl 383 —CH₂— pyridin-4,2-diyl bond2,4-diCl-phenyl 384 —CH₂— pyridin-4,2-diyl bond 2,5-diCl-phenyl 385—CH₂— pyridin-4,2-diyl bond 2,6-diCl-phenyl 386 —CH₂— pyridin-4,2-diylbond 3,4-diCl-phenyl 387 —CH₂— pyridin-4,2-diyl bond 3,5-diCl-phenyl 388—CH₂— pyridin-4,2-diyl bond 2-Cl-3-F-phenyl 389 —CH₂— pyridin-4,2-diylbond 2-Cl-4-F-phenyl 390 —CH₂— pyridin-4,2-diyl bond 2-Cl-5-F-phenyl 391—CH₂— pyridin-4,2-diyl bond 3-Cl-4-F-phenyl 392 —CH₂— pyridin-4,2-diylbond 3-Cl-5-F-phenyl 393 —CH₂— pyridin-4,2-diyl bond 4-Cl-2-F-phenyl 394—CH₂— pyridin-4,2-diyl bond 4-Cl-3-F-phenyl 395 —CH₂— pyridin-4,2-diylbond 2,3-diMeO-phenyl 396 —CH₂— pyridin-4,2-diyl bond 2,4-diMeO-phenyl397 —CH₂— pyridin-4,2-diyl bond 2,5-diMeO-phenyl 398 —CH₂—pyridin-4,2-diyl bond 2,6-diMeO-phenyl 399 —CH₂— pyridin-4,2-diyl bond3,4-diMeO-phenyl 400 —CH₂— pyridin-4,2-diyl bond 3,5-diMeO-phenyl 401—CH₂— pyridin-4,2-diyl bond cyclopropyl 402 —CH₂— pyridin-4,2-diyl bondcyclobutyl 403 —CH₂— pyridin-4,2-diyl bond cyclopentyl 404 —CH₂—pyridin-4,2-diyl bond cyclohexyl 405 —CH₂— pyridin-4,2-diyl bond2-furanyl 406 —CH₂— pyridin-4,2-diyl bond 2-thienyl 407 —CH₂—pyridin-4,2-diyl bond 2-imidazolyl 408 —CH₂— pyridin-4,2-diyl bond2-pyridyl 409 —CH₂— pyridin-4,2-diyl bond 3-pyridyl 410 —CH₂—pyridin-4,2-diyl bond 4-pyridyl 411 —CH₂— pyridin-4,2-diyl bondN-morpholinyl 412 —CH₂— pyridin-4,2-diyl bond N-piperidinyl 413 —CH₂—pyridin-4,2-diyl bond 3-Me-2-pyridyl 414 —CH₂— pyridin-4,2-diyl bond4-Me-2-pyridyl 415 —CH₂— pyridin-4,2-diyl bond 1-indolyl 416 —CH₂—pyridin-4,2-diyl bond 2-benzothienyl 417 —CH₂— pyridin-4,2-diyl bond2-benzofuranyl 418 —CH₂— pyridin-4,2-diyl bond 1-benzimidazole 419 —CH₂—pyridin-4,2-diyl bond 2-naphthyl 420 —CH₂— piperidin-1,3-diyl bondphenyl 421 —CH₂— piperidin-1,3-diyl bond 3,3-diphenylmethyl 422 —CH₂—piperidin-1,3-diyl bond 2-F-phenyl 423 —CH₂— piperidin-1,3-diyl bond3-F-phenyl 424 —CH₂— piperidin-1,3-diyl bond 4-F-phenyl 425 —CH₂—piperidin-1,3-diyl bond 2-Cl-phenyl 426 —CH₂— piperidin-1,3-diyl bond3-Cl-phenyl 427 —CH₂— piperidin-1,3-diyl bond 4-Cl-phenyl 428 —CH₂—piperidin-1,3-diyl bond 2-Me-phenyl 429 —CH₂— piperidin-1,3-diyl bond3-Me-phenyl 430 —CH₂— piperidin-1,3-diyl bond 4-Me-phenyl 431 —CH₂—piperidin-1,3-diyl bond 2-MeO-phenyl 432 —CH₂— piperidin-1,3-diyl bond3-MeO-phenyl 433 —CH₂— piperidin-1,3-diyl bond 4-MeO-phenyl 434 —CH₂—piperidin-1,3-diyl bond 2-MeS-phenyl 435 —CH₂— piperidin-1,3-diyl bond3-MeS-phenyl 436 —CH₂— piperidin-1,3-diyl bond 4-MeS-phenyl 437 —CH₂—piperidin-1,3-diyl bond 2-F₃C-phenyl 438 —CH₂— piperidin-1,3-diyl bond3-F₃C-phenyl 439 —CH₂— piperidin-1,3-diyl bond 4-F₃C-phenyl 440 —CH₂—piperidin-1,3-diyl bond 2,3-diF-phenyl 441 —CH₂— piperidin-1,3-diyl bond2,4-diF-phenyl 442 —CH₂— piperidin-1,3-diyl bond 2,5-diF-phenyl 443—CH₂— piperidin-1,3-diyl bond 2,6-diF-phenyl 444 —CH₂—piperidin-1,3-diyl bond 3,4-diF-phenyl 445 —CH₂— piperidin-1,3-diyl bond3,5-diF-phenyl 446 —CH₂— piperidin-1,3-diyl bond 2,3-diCl-phenyl 447—CH₂— piperidin-1,3-diyl bond 2,4-diCl-phenyl 448 —CH₂—piperidin-1,3-diyl bond 2,5-diCl-phenyl 449 —CH₂— piperidin-1,3-diylbond 2,6-diCl-phenyl 450 —CH₂— piperidin-1,3-diyl bond 3,4-diCl-phenyl451 —CH₂— piperidin-1,3-diyl bond 3,5-diCl-phenyl 452 —CH₂—piperidin-1,3-diyl bond 2-Cl-3-F-phenyl 453 —CH₂— piperidin-1,3-diylbond 2-Cl-4-F-phenyl 454 —CH₂— piperidin-1,3-diyl bond 2-Cl-5-F-phenyl455 —CH₂— piperidin-1,3-diyl bond 3-Cl-4-F-phenyl 456 —CH₂—piperidin-1,3-diyl bond 3-Cl-5-F-phenyl 457 —CH₂— piperidin-1,3-diylbond 4-Cl-2-F-phenyl 458 —CH₂— piperidin-1,3-diyl bond 4-Cl-3-F-phenyl459 —CH₂— piperidin-1,3-diyl bond 2,3-diMeO-phenyl 460 —CH₂—piperidin-1,3-diyl bond 2,4-diMeO-phenyl 461 —CH₂— piperidin-1,3-diylbond 2,5-diMeO-phenyl 462 —CH₂— piperidin-1,3-diyl bond 2,6-diMeO-phenyl463 —CH₂— piperidin-1,3-diyl bond 3,4-diMeO-phenyl 464 —CH₂—piperidin-1,3-diyl bond 3,5-diMeO-phenyl 465 —CH₂— piperidin-1,3-diylbond cyclopropyl 466 —CH₂— piperidin-1,3-diyl bond cyclobutyl 467 —CH₂—piperidin-1,3-diyl bond cyclopentyl 468 —CH₂— piperidin-1,3-diyl bondcyclohexyl 469 —CH₂— piperidin-1,3-diyl bond 2-furanyl 470 —CH₂—piperidin-1,3-diyl bond 2-thienyl 471 —CH₂— piperidin-1,3-diyl bond2-imidazolyl 472 —CH₂— piperidin-1,3-diyl bond 2-pyridyl 473 —CH₂—piperidin-1,3-diyl bond 3-pyridyl 474 —CH₂— piperidin-1.3-diyl bond4-pyridyl 475 —CH₂— piperidin-1,3-diyl bond N-morpholinyl 476 —CH₂—piperidin-1,3-diyl bond N-piperidinyl 477 —CH₂— piperidin-1,3-diyl bond3-Me-2-pyridyl 478 —CH₂— piperidin-1,3-diyl bond 4-Me-2-pyridyl 479—CH₂— piperidin-1,3-diyl bond 1-indolyl 480 —CH₂— piperidin-1,3-diylbond 2-benzothienyl 481 —CH₂— piperidin-1,3-diyl bond 2-benzofuranyl 482—CH₂— piperidin-1,3-diyl bond 1-benzimidazole 483 —CH₂—piperidin-1,3-diyl bond 2-naphthyl 484 —CH₂— piperidin-3,1-diyl bondphenyl 485 —CH₂— piperidin-3,1-diyl bond 3,3-diphenylmethyl 486 —CH₂—piperidin-3,1-diyl bond 2-F-phenyl 487 —CH₂— piperidin-3,1-diyl bond3-F-phenyl 488 —CH₂— piperidin-3,1-diyl bond 4-F-phenyl 489 —CH₂—piperidin-3,1-diyl bond 2-Cl-phenyl 490 —CH₂— piperidin-3,1-diyl bond3-Cl-phenyl 491 —CH₂— piperidin-3,1-diyl bond 4-Cl-phenyl 492 —CH₂—piperidin-3,1-diyl bond 2-Me-phenyl 493 —CH₂— piperidin-3,1-diyl bond3-Me-phenyl 494 —CH₂— piperidin-3,1-diyl bond 4-Me-phenyl 495 —CH₂—piperidin-3,1-diyl bond 2-MeO-phenyl 496 —CH₂— piperidin-3,1-diyl bond3-MeO-phenyl 497 —CH₂— piperidin-3,1-diyl bond 4-MeO-phenyl 498 —CH₂—piperidin-3,1-diyl bond 2-MeS-phenyl 499 —CH₂— piperidin-3,1-diyl bond3-MeS-phenyl 500 —CH₂— piperidin-3,1-diyl bond 4-MeS-phenyl 501 —CH₂—piperidin-3,1-diyl bond 2-F₃C-phenyl 502 —CH₂— piperidin-3,1-diyl bond3-F₃C-phenyl 503 —CH₂— piperidin-3,1-diyl bond 4-F₃C-phenyl 504 —CH₂—piperidin-3,1-diyl bond 2,3-diF-phenyl 505 —CH₂— piperidin-3,1-diyl bond2,4-diF-phenyl 506 —CH₂— piperidin-3,1-diyl bond 2,5-diF-phenyl 507—CH₂— piperidin-3,1-diyl bond 2,6-diF-phenyl 508 —CH₂—piperidin-3,1-diyl bond 3,4-diF-phenyl 509 —CH₂— piperidin-3,1-diyl bond3,5-diF-phenyl 510 —CH₂— piperidin-3,1-diyl bond 2,3-diCl-phenyl 511—CH₂— piperidin-3,1-diyl bond 2,4-diCl-phenyl 512 —CH₂—piperidin-3,1-diyl bond 2,5-diCl-phenyl 513 —CH₂— piperidin-3,1-diylbond 2,6-diCl-phenyl 514 —CH₂— piperidin-3,1-diyl bond 3,4-diCl-phenyl515 —CH₂— piperidin-3,1-diyl bond 3,5-diCl-phenyl 516 —CH₂—piperidin-3,1-diyl bond 2-Cl-3-F-phenyl 517 —CH₂— piperidin-3,1-diylbond 2-Cl-4-F-phenyl 518 —CH₂— piperidin-3,1-diyl bond 2-Cl-5-F-phenyl519 —CH₂— piperidin-3,1-diyl bond 3-Cl-4-F-phenyl 520 —CH₂—piperidin-3,1-diyl bond 3-Cl-5-F-phenyl 521 —CH₂— piperidin-3,1-diylbond 4-Cl-2-F-phenyl 522 —CH₂— piperidin-3,1-diyl bond 4-Cl-3-F-phenyl523 —CH₂— piperidin-3,1-diyl bond 2,3-diMeO-phenyl 524 —CH₂—piperidin-3,1-diyl bond 2,4-diMeO-phenyl 525 —CH₂— piperidin-3,1-diylbond 2,5-diMeO-phenyl 526 —CH₂— piperidin-3,1-diyl bond 2,6-diMeO-phenyl527 —CH₂— piperidin-3,1-diyl bond 3,4-diMeO-phenyl 528 —CH₂—piperidin-3,1-diyl bond 3,5-diMeO-phenyl 529 —CH₂— piperidin-3,1-diylbond cyclopropyl 530 —CH₂— piperidin-3,1-diyl bond cyclobutyl 531 —CH₂—piperidin-3,1-diyl bond cyclopentyl 532 —CH₂— piperidin-3,1-diyl bondcyclohexyl 533 —CH₂— piperidin-3,1-diyl bond 2-furanyl 534 —CH₂—piperidin-3,1-diyl bond 2-thienyl 535 —CH₂— piperidin-3,1-diyl bond2-imidazolyl 536 —CH₂— piperidin-3,1-diyl bond 2-pyridyl 537 —CH₂—piperidin-3,1-diyl bond 3-pyridyl 538 —CH₂— piperidin-3,1-diyl bond4-pyridyl 539 —CH₂— piperidin-3,1-diyl bond N-morpholinyl 540 —CH₂—piperidin-3,1-diyl bond N-piperidinyl 541 —CH₂— piperidin-3,1-diyl bond3-Me-2-pyridyl 542 —CH₂— piperidin-3,1-diyl bond 4-Me-2-pyridyl 543—CH₂— piperidin-3,1-diyl bond 1-indolyl 544 —CH₂— piperidin-3,1-diylbond 2-benzothienyl 545 —CH₂— piperidin-3,1-diyl bond 2-benzofuranyl 546—CH₂— piperidin-3,1-diyl bond 1-benzimidazole 547 —CH₂—piperidin-3,1-diyl bond 2-naphthyl 548 —CH₂— cyclohex-1,3-diyl bondphenyl 549 —CH₂— cyclohex-1,3-diyl bond 3,3-diphenylmethyl 550 —CH₂—cyclohex-1,3-diyl bond 2-F-phenyl 551 —CH₂— cyclohex-1,3-diyl bond3-F-phenyl 552 —CH₂— cyclohex-1,3-diyl bond 4-F-phenyl 553 —CH₂—cyclohex-1,3-diyl bond 2-Cl-phenyl 554 —CH₂— cyclohex-1,3-diyl bond3-Cl-phenyl 555 —CH₂— cyclohex-1,3-diyl bond 4-Cl-phenyl 556 —CH₂—cyclohex-1,3-diyl bond 2-Me-phenyl 557 —CH₂— cyclohex-1,3-diyl bond3-Me-phenyl 558 —CH₂— cyclohex-1,3-diyl bond 4-Me-phenyl 559 —CH₂—cyclohex-1,3-diyl bond 2-MeO-phenyl 560 —CH₂— cyclohex-1,3-diyl bond3-MeO-phenyl 561 —CH₂— cyclohex-1,3-diyl bond 4-MeO-phenyl 562 —CH₂—cyclohex-1,3-diyl bond 2-MeS-phenyl 563 —CH₂— cyclohex-1,3-diyl bond3-MeS-phenyl 564 —CH₂— cyclohex-1,3-diyl bond 4-MeS-phenyl 565 —CH₂—cyclohex-1,3-diyl bond 2-F₃C-phenyl 566 —CH₂— cyclohex-1,3-diyl bond3-F₃C-phenyl 567 —CH₂— cyclohex-1,3-diyl bond 4-F₃C-phenyl 568 —CH₂—cyclohex-1,3-diyl bond 2,3-diF-phenyl 569 —CH₂— cyclohex-1,3-diyl bond2,4-diF-phenyl 570 —CH₂— cyclohex-1,3-diyl bond 2,5-diF-phenyl 571 —CH₂—cyclohex-1,3-diyl bond 2,6-diF-phenyl 572 —CH₂— cyclohex-1,3-diyl bond3,4-diF-phenyl 573 —CH₂— cyclohex-1,3-diyl bond 3,5-diF-phenyl 574 —CH₂—cyclohex-1,3-diyl bond 2,3-diCl-phenyl 575 —CH₂— cyclohex-1,3-diyl bond2,4-diCl-phenyl 576 —CH₂— cyclohex-1,3-diyl bond 2,5-diCl-phenyl 577—CH₂— cyclohex-1,3-diyl bond 2,6-diCl-phenyl 578 —CH₂— cyclohex-1,3-diylbond 3,4-diCl-phenyl 579 —CH₂— cyclohex-1,3-diyl bond 3,5-diCl-phenyl580 —CH₂— cyclohex-1,3-diyl bond 2-Cl-3-F-phenyl 581 —CH₂—cyclohex-1,3-diyl bond 2-Cl-4-F-phenyl 582 —CH₂— cyclohex-1,3-diyl bond2-Cl-5-F-phenyl 583 —CH₂— cyclohex-1,3-diyl bond 3-Cl-4-F-phenyl 584—CH₂— cyclohex-1,3-diyl bond 3-Cl-5-F-phenyl 585 —CH₂— cyclohex-1,3-diylbond 4-Cl-2-F-phenyl 586 —CH₂— cyclohex-1,3-diyl bond 4-Cl-3-F-phenyl587 —CH₂— cyclohex-1,3-diyl bond 2,3-diMeO-phenyl 588 —CH₂—cyclohex-1,3-diyl bond 2,4-diMeO-phenyl 589 —CH₂— cyclohex-1,3-diyl bond2,5-diMeO-phenyl 590 —CH₂— cyclohex-1,3-diyl bond 2,6-diMeO-phenyl 591—CH₂— cyclohex-1,3-diyl bond 3,4-diMeO-phenyl 592 —CH₂—cyclohex-1,3-diyl bond 3,5-diMeO-phenyl 593 —CH₂— cyclohex-1,3-diyl bondcyclopropyl 594 —CH₂— cyclohex-1,3-diyl bond cyclobutyl 595 —CH₂—cyclohex-1,3-diyl bond cyclopentyl 596 —CH₂— cyclohex-1,3-diyl bondcyclohexyl 597 —CH₂— cyclohex-1,3-diyl bond 2-furanyl 598 —CH₂—cyclohex-1,3-diyl bond 2-thienyl 599 —CH₂— cyclohex-1,3-diyl bond2-imidazolyl 600 —CH₂— cyclohex-1,3-diyl bond 2-pyridyl 601 —CH₂—cyclohex-1,3-diyl bond 3-pyridyl 602 —CH₂— cyclohex-1,3-diyl bond4-pyridyl 603 —CH₂— cyclohex-1,3-diyl bond N-morpholinyl 604 —CH₂—cyclohex-1,3-diyl bond N-piperidinyl 605 —CH₂— cyclohex-1,3-diyl bond3-Me-2-pyridyl 606 —CH₂— cyclohex-1,3-diyl bond 4-Me-2-pyridyl 607 —CH₂—cyclohex-1,3-diyl bond 1-indolyl 608 —CH₂— cyclohex-1,3-diyl bond2-benzothienyl 609 —CH₂— cyclohex-1,3-diyl bond 2-benzofuranyl 610 —CH₂—cyclohex-1,3-diyl bond 1-benzimidazole 611 —CH₂— cyclohex-1,3-diyl bond2-naphthyl 612 —CH₂— cyclopropan-1,2-diyl bond phenyl 613 —CH₂—cyclopropan-1,2-diyl bond 3,3-diphenylmethyl 614 —CH₂—cyclopropan-1,2-diyl bond 2-F-phenyl 615 —CH₂— cyclopropan-1,2-diyl bond3-F-phenyl 616 —CH₂— cyclopropan-1,2-diyl bond 4-F-phenyl 617 —CH₂—cyclopropan-1,2-diyl bond 2-Cl-phenyl 618 —CH₂— cyclopropan-1,2-diylbond 3-Cl-phenyl 619 —CH₂— cyclopropan-1,2-diyl bond 4-Cl-phenyl 620—CH₂— cyclopropan-1,2-diyl bond 2-Me-phenyl 621 —CH₂—cyclopropan-1,2-diyl bond 3-Me-phenyl 622 —CH₂— cyclopropan-1,2-diylbond 4-Me-phenyl 623 —CH₂— cyclopropan-1,2-diyl bond 2-MeO-phenyl 624—CH₂— cyclopropan-1,2-diyl bond 3-MeO-phenyl 625 —CH₂—cyclopropan-1,2-diyl bond 4-MeO-phenyl 626 —CH₂— cyclopropan-1,2-diylbond 2-MeS-phenyl 627 —CH₂— cyclopropan-1,2-diyl bond 3-MeS-phenyl 628—CH₂— cyclopropan-1,2-diyl bond 4-MeS-phenyl 629 —CH₂—cyclopropan-1,2-diyl bond 2-F₃C-phenyl 630 —CH₂— cyclopropan-1,2-diylbond 3-F₃C-phenyl 631 —CH₂— cyclopropan-1,2-diyl bond 4-F₃C-phenyl 632—CH₂— cyclopropan-1,2-diyl bond 2,3-diF-phenyl 633 —CH₂—cyclopropan-1,2-diyl bond 2,4-diF-phenyl 634 —CH₂— cyclopropan-1,2-diylbond 2,5-diF-phenyl 635 —CH₂— cyclopropan-1,2-diyl bond 2,6-diF-phenyl636 —CH₂— cyclopropan-1,2-diyl bond 3,4-diF-phenyl 637 —CH₂—cyclopropan-1,2-diyl bond 3,5-diF-phenyl 638 —CH₂— cyclopropan-1,2-diylbond 2,3-diCl-phenyl 639 —CH₂— cyclopropan-1,2-diyl bond 2,4-diCl-phenyl640 —CH₂— cyclopropan-1,2-diyl bond 2,5-diCl-phenyl 641 —CH₂—cyclopropan-1,2-diyl bond 2,6-diCl-phenyl 642 —CH₂— cyclopropan-1,2-diylbond 3,4-diCl-phenyl 643 —CH₂— cyclopropan-1,2-diyl bond 3,5-diCl-phenyl644 —CH₂— cyclopropan-1,2-diyl bond 2-Cl-3-F-phenyl 645 —CH₂—cyclopropan-1,2-diyl bond 2-Cl-4-F-phenyl 646 —CH₂— cyclopropan-1,2-diylbond 2-Cl-5-F-phenyl 647 —CH₂— cyclopropan-1,2-diyl bond 3-Cl-4-F-phenyl648 —CH₂— cyclopropan-1,2-diyl bond 3-Cl-5-F-phenyl 649 —CH₂—cyclopropan-1,2-diyl bond 4-Cl-2-F-phenyl 650 —CH₂— cyclopropan-1,2-diylbond 4-Cl-3-F-phenyl 651 —CH₂— cyclopropan-1,2-diyl bond2,3-diMeO-phenyl 652 —CH₂— cyclopropan-1,2-diyl bond 2,4-diMeO-phenyl653 —CH₂— cyclopropan-1,2-diyl bond 2,5-diMeO-phenyl 654 —CH₂—cyclopropan-1,2-diyl bond 2,6-diMeO-phenyl 655 —CH₂—cyclopropan-1,2-diyl bond 3,4-diMeO-phenyl 656 —CH₂—cyclopropan-1,2-diyl bond 3,5-diMeO-phenyl 657 —CH₂—cyclopropan-1,2-diyl bond cyclopropyl 658 —CH₂— cyclopropan-1,2-diylbond cyclobutyl 659 —CH₂— cyclopropan-1,2-diyl bond cyclopentyl 660—CH₂— cyclopropan-1,2-diyl bond cyclohexyl 661 —CH₂—cyclopropan-1,2-diyl bond 2-furanyl 662 —CH₂— cyclopropan-1,2-diyl bond2-thienyl 663 —CH₂— cyclopropan-1,2-diyl bond 2-imidazolyl 664 —CH₂—cyclopropan-1,2-diyl bond 2-pyridyl 665 —CH₂— cyclopropan-1,2-diyl bond3-pyridyl 666 —CH₂— cyclopropan-1,2-diyl bond 4-pyridyl 667 —CH₂—cyclopropan-1,2-diyl bond N-morpholinyl 668 —CH₂— cyclopropan-1,2-diylbond N-piperidinyl 669 —CH₂— cyclopropan-1,2-diyl bond 3-Me-2-pyridyl670 —CH₂— cyclopropan-1,2-diyl bond 4-Me-2-pyridyl 671 —CH₂—cyclopropan-1,2-diyl bond 1-indolyl 672 —CH₂— cyclopropan-1,2-diyl bond2-benzothienyl 673 —CH₂— cyclopropan-1,2-diyl bond 2-benzofuranyl 674—CH₂— cyclopropan-1,2-diyl bond 1-benzimidazole 675 —CH₂—cyclopropan-1,2-diyl bond 2-naphthyl 676 —CH₂— cyclopentan-1,3-diyl bondphenyl 677 —CH₂— cyclopentan-1,3-diyl bond 3,3-diphenylmethyl 678 —CH₂—cyclopentan-1,3-diyl bond 2-F-phenyl 679 —CH₂— cyclopentan-1,3-diyl bond3-F-phenyl 680 —CH₂— cyclopentan-1,3-diyl bond 4-F-phenyl 681 —CH₂—cyclopentan-1,3-diyl bond 2-Cl-phenyl 682 —CH₂— cyclopentan-1,3-diylbond 3-Cl-phenyl 683 —CH₂— cyclopentan-1,3-diyl bond 4-Cl-phenyl 684—CH₂— cyclopentan-1,3-diyl bond 2-Me-phenyl 685 —CH₂—cyclopentan-1,3-diyl bond 3-Me-phenyl 686 —CH₂— cyclopentan-1,3-diylbond 4-Me-phenyl 687 —CH₂— cyclopentan-1,3-diyl bond 2-MeO-phenyl 688—CH₂— cyclopentan-1,3-diyl bond 3-MeO-phenyl 689 —CH₂—cyclopentan-1,3-diyl bond 4-MeO-phenyl 690 —CH₂— cyclopentan-1,3-diylbond 2-MeS-phenyl 691 —CH₂— cyclopentan-1,3-diyl bond 3-MeS-phenyl 692—CH₂— cyclopentan-1,3-diyl bond 4-MeS-phenyl 693 —CH₂—cyclopentan-1,3-diyl bond 2-F₃C-phenyl 694 —CH₂— cyclopentan-1,3-diylbond 3-F₃C-phenyl 695 —CH₂— cyclopentan-1,3-diyl bond 4-F₃C-phenyl 696—CH₂— cyclopentan-1,3-diyl bond 2,3-diF-phenyl 697 —CH₂—cyclopentan-1,3-diyl bond 2,4-diF-phenyl 698 —CH₂— cyclopentan-1,3-diylbond 2,5-diF-phenyl 699 —CH₂— cyclopentan-1,3-diyl bond 2,6-diF-phenyl700 —CH₂— cyclopentan-1,3-diyl bond 3,4-diF-phenyl 701 —CH₂—cyclopentan-1,3-diyl bond 3,5-diF-phenyl 702 —CH₂— cyclopentan-1,3-diylbond 2,3-diCl-phenyl 703 —CH₂— cyclopentan-1,3-diyl bond 2,4-diCl-phenyl704 —CH₂— cyclopentan-1,3-diyl bond 2,5-diCl-phenyl 705 —CH₂—cyclopentan-1,3-diyl bond 2,6-diCl-phenyl 706 —CH₂— cyclopentan-1,3-diylbond 3,4-diCl-phenyl 707 —CH₂— cyclopentan-1,3-diyl bond 3,5-diCl-phenyl708 —CH₂— cyclopentan-1,3-diyl bond 2-Cl-3-F-phenyl 709 —CH₂—cyclopentan-1,3-diyl bond 2-Cl-4-F-phenyl 710 —CH₂— cyclopentan-1,3-diylbond 2-Cl-5-F-phenyl 711 —CH₂— cyclopentan-1,3-diyl bond 3-Cl-4-F-phenyl712 —CH₂— cyclopentan-1,3-diyl bond 3-Cl-5-F-phenyl 713 —CH₂—cyclopentan-1,3-diyl bond 4-Cl-2-F-phenyl 714 —CH₂— cyclopentan-1,3-diylbond 4-Cl-3-F-phenyl 715 —CH₂— cyclopentan-1,3-diyl bond2,3-diMeO-phenyl 716 —CH₂— cyclopentan-1,3-diyl bond 2,4-diMeO-phenyl717 —CH₂— cyclopentan-1,3-diyl bond 2,5-diMeO-phenyl 718 —CH₂—cyclopentan-1,3-diyl bond 2,6-diMeO-phenyl 719 —CH₂—cyclopentan-1,3-diyl bond 3,4-diMeO-phenyl 720 —CH₂—cyclopentan-1,3-diyl bond 3,5-diMeO-phenyl 721 —CH₂—cyclopentan-1,3-diyl bond cyclopropyl 722 —CH₂— cyclopentan-1,3-diylbond cyclobutyl 723 —CH₂— cyclopentan-1,3-diyl bond cyclopentyl 724—CH₂— cyclopentan-1,3-diyl bond cyclohexyl 725 —CH₂—cyclopentan-1,3-diyl bond 2-furanyl 726 —CH₂— cyclopentan-1,3-diyl bond2-thienyl 727 —CH₂— cyclopentan-1,3-diyl bond 2-imidazolyl 728 —CH₂—cyclopentan-1,3-diyl bond 2-pyridyl 729 —CH₂— cyclopentan-1,3-diyl bond3-pyridyl 730 —CH₂— cyclopentan-1,3-diyl bond 4-pyridyl 731 —CH₂—cyclopentan-1,3-diyl bond N-morpholinyl 732 —CH₂— cyclopentan-1,3-diylbond N-piperidinyl 733 —CH₂— cyclopentan-1,3-diyl bond 3-Me-2-pyridyl734 —CH₂— cyclopentan-1,3-diyl bond 4-Me-2-pyridyl 735 —CH₂—cyclopentan-1,3-diyl bond 1-indolyl 736 —CH₂— cyclopentan-1,3-diyl bond2-benzothienyl 737 —CH₂— cyclopentan-1,3-diyl bond 2-benzofuranyl 738—CH₂— cyclopentan-1,3-diyl bond 1-benzimidazole 739 —CH₂—cyclopentan-1,3-diyl bond 2-naphthyl 740 —CH₂— phen-1,3-diyl —O— phenyl741 —CH₂— phen-1,3-diyl —O— 3,3-diphenylmethyl 742 —CH₂— phen-1,3-diyl—O— 2-F-phenyl 743 —CH₂— phen-1,3-diyl —O— 3-F-phenyl 744 —CH₂—phen-1,3-diyl —O— 4-F-phenyl 745 —CH₂— phen-1,3-diyl —O— 2-Cl-phenyl 746—CH₂— phen-1,3-diyl —O— 3-Cl-phenyl 747 —CH₂— phen-1,3-diyl —O—4-Cl-phenyl 748 —CH₂— phen-1,3-diyl —O— 2-Me-phenyl 749 —CH₂—phen-1,3-diyl —O— 3-Me-phenyl 750 —CH₂— phen-1,3-diyl —O— 4-Me-phenyl751 —CH₂— phen-1,3-diyl —O— 2-MeO-phenyl 752 —CH₂— phen-1,3-diyl —O—3-MeO-phenyl 753 —CH₂— phen-1,3-diyl —O— 4-MeO-phenyl 754 —CH₂—phen-1,3-diyl —O— 2-MeS-phenyl 755 —CH₂— phen-1,3-diyl —O— 3-MeS-phenyl756 —CH₂— phen-1,3-diyl —O— 4-MeS-phenyl 757 —CH₂— phen-1,3-diyl —O—2-F₃C-phenyl 758 —CH₂— phen-1,3-diyl —O— 3-F₃C-phenyl 759 —CH₂—phen-1,3-diyl —O— 4-F₃C-phenyl 760 —CH₂— phen-1,3-diyl —O—2,3-diF-phenyl 761 —CH₂— phen-1,3-diyl —O— 2,4-diF-phenyl 762 —CH₂—phen-1,3-diyl —O— 2,5-diF-phenyl 763 —CH₂— phen-1,3-diyl —O—2,6-diF-phenyl 764 —CH₂— phen-1,3-diyl —O— 3,4-diF-phenyl 765 —CH₂—phen-1,3-diyl —O— 3,5-diF-phenyl 766 —CH₂— phen-1,3-diyl —O—2,3-diCl-phenyl 767 —CH₂— phen-1,3-diyl —O— 2,4-diCl-phenyl 768 —CH₂—phen-1,3-diyl —O— 2,5-diCl-phenyl 769 —CH₂— phen-1,3-diyl —O—2,6-diCl-phenyl 770 —CH₂— phen-1,3-diyl —O— 3,4-diCl-phenyl 771 —CH₂—phen-1,3-diyl —O— 3,5-diCl-phenyl 772 —CH₂— phen-1,3-diyl —O—2-Cl-3-F-phenyl 773 —CH₂— phen-1,3-diyl —O— 2-Cl-4-F-phenyl 774 —CH₂—phen-1,3-diyl —O— 2-Cl-5-F-phenyl 775 —CH₂— phen-1,3-diyl —O—3-Cl-4-F-phenyl 776 —CH₂— phen-1,3-diyl —O— 3-Cl-5-F-phenyl 777 —CH₂—phen-1,3-diyl —O— 4-Cl-2-F-phenyl 778 —CH₂— phen-1,3-diyl —O—4-Cl-3-F-phenyl 779 —CH₂— phen-1,3-diyl —O— 2,3-diMeO-phenyl 780 —CH₂—phen-1,3-diyl —O— 2,4-diMeO-phenyl 781 —CH₂— phen-1,3-diyl —O—2,5-diMeO-phenyl 782 —CH₂— phen-1,3-diyl —O— 2,6-diMeO-phenyl 783 —CH₂—phen-1,3-diyl —O— 3,4-diMeO-phenyl 784 —CH₂— phen-1,3-diyl —O—3,5-diMeO-phenyl 785 —CH₂— phen-1,3-diyl —O— cyclopropyl 786 —CH₂—phen-1,3-diyl —O— cyclobutyl 787 —CH₂— phen-1,3-diyl —O— cyclopentyl 788—CH₂— phen-1,3-diyl —O— cyclohexyl 789 —CH₂— phen-1,3-diyl —O— 2-furanyl790 —CH₂— phen-1,3-diyl —O— 2-thienyl 791 —CH₂— phen-1,3-diyl CH₂CH₂2-imidazolyl 792 —CH₂— phen-1,3-diyl —O— 2-pyridyl 793 —CH₂—phen-1,3-diyl —O— 3-pyridyl 794 —CH₂— phen-1,3-diyl —O— 4-pyridyl 795—CH₂— phen-1,3-diyl CH₂CH₂ N-morpholinyl 796 —CH₂— phen-1,3-diyl CH₂CH₂N-piperidinyl 797 —CH₂— phen-1,3-diyl —O— 3-Me-2-pyridyl 798 —CH₂—phen-1,3-diyl —O— 4-Me-2-pyridyl 799 —CH₂— phen-1,3-diyl CH₂CH₂1-indolyl 800 —CH₂— phen-1,3-diyl —O— 2-benzothienyl 801 —CH₂—phen-1,3-diyl —O— 2-benzofuranyl 802 —CH₂— phen-1,3-diyl CH₂CH₂1-benzimidazole 803 —CH₂— phen-1,3-diyl —O— 2-naphthyl 804 —CH₂—pyridin-3,5-diyl —O— phenyl 805 —CH₂— pyridin-3,5-diyl —O—3,3-diphenylmethyl 806 —CH₂— pyridin-3,5-diyl —O— 2-F-phenyl 807 —CH₂—pyridin-3,5-diyl —O— 3-F-phenyl 808 —CH₂— pyridin-3,5-diyl —O—4-F-phenyl 809 —CH₂— pyridin-3,5-diyl —O— 2-Cl-phenyl 810 —CH₂—pyridin-3,5-diyl —O— 3-Cl-phenyl 811 —CH₂— pyridin-3,5-diyl —O—4-Cl-phenyl 812 —CH₂— pyridin-3,5-diyl —O— 2-Me-phenyl 813 —CH₂—pyridin-3,5-diyl —O— 3-Me-phenyl 814 —CH₂— pyridin-3,5-diyl —O—4-Me-phenyl 815 —CH₂— pyridin-3,5-diyl —O— 2-MeO-phenyl 816 —CH₂—pyridin-3,5-diyl —O— 3-MeO-phenyl 817 —CH₂— pyridin-3,5-diyl —O—4-MeO-phenyl 818 —CH₂— pyridin-3,5-diyl —O— 2-MeS-phenyl 819 —CH₂—pyridin-3,5-diyl —O— 3-MeS-phenyl 820 —CH₂— pyridin-3,5-diyl —O—4-MeS-phenyl 821 —CH₂— pyridin-3,5-diyl —O— 2-F₃C-phenyl 822 —CH₂—pyridin-3,5-diyl —O— 3-F₃C-phenyl 823 —CH₂— pyridin-3,5-diyl —O—4-F₃C-phenyl 824 —CH₂— pyridin-3,5-diyl —O— 2,3-diF-phenyl 825 —CH₂—pyridin-3,5-diyl —O— 2,4-diF-phenyl 826 —CH₂— pyridin-3,5-diyl —O—2,5-diF-phenyl 827 —CH₂— pyridin-3,5-diyl —O— 2,6-diF-phenyl 828 —CH₂—pyridin-3,5-diyl —O— 3,4-diF-phenyl 829 —CH₂— pyridin-3,5-diyl —O—3,5-diF-phenyl 830 —CH₂— pyridin-3,5-diyl —O— 2,3-diCl-phenyl 831 —CH₂—pyridin-3,5-diyl —O— 2,4-diCl-phenyl 832 —CH₂— pyridin-3,5-diyl —O—2,5-diCl-phenyl 833 —CH₂— pyridin-3,5-diyl —O— 2,6-diCl-phenyl 834 —CH₂—pyridin-3,5-diyl —O— 3,4-diCl-phenyl 835 —CH₂— pyridin-3,5-diyl —O—3,5-diCl-phenyl 836 —CH₂— pyridin-3,5-diyl —O— 2-Cl-3-F-phenyl 837 —CH₂—pyridin-3,5-diyl —O— 2-Cl-4-F-phenyl 838 —CH₂— pyridin-3,5-diyl —O—2-Cl-5-F-phenyl 839 —CH₂— pyridin-3,5-diyl —O— 3-Cl-4-F-phenyl 840 —CH₂—pyridin-3,5-diyl —O— 3-Cl-5-F-phenyl 841 —CH₂— pyridin-3,5-diyl —O—4-Cl-2-F-phenyl 842 —CH₂— pyridin-3,5-diyl —O— 4-Cl-3-F-phenyl 843 —CH₂—pyridin-3,5-diyl —O— 2,3-diMeO-phenyl 844 —CH₂— pyridin-3,5-diyl —O—2,4-diMeO-phenyl 845 —CH₂— pyridin-3,5-diyl —O— 2,5-diMeO-phenyl 846—CH₂— pyridin-3,5-diyl —O— 2,6-diMeO-phenyl 847 —CH₂— pyridin-3,5-diyl—O— 3,4-diMeO-phenyl 848 —CH₂— pyridin-3,5-diyl —O— 3,5-diMeO-phenyl 849—CH₂— pyridin-3,5-diyl —O— cyclopropyl 850 —CH₂— pyridin-3,5-diyl —O—cyclobutyl 851 —CH₂— pyridin-3,5-diyl —O— cyclopentyl 852 —CH₂—pyridin-3,5-diyl —O— cyclohexyl 853 —CH₂— pyridin-3,5-diyl —O— 2-furanyl854 —CH₂— pyridin-3,5-diyl —O— 2-thienyl 855 —CH₂— pyridin-3,5-diylCH₂CH₂ 2-imidazolyl 856 —CH₂— pyridin-3,5-diyl —O— 2-pyridyl 857 —CH₂—pyridin-3,5-diyl —O— 3-pyridyl 858 —CH₂— pyridin-3,5-diyl —O— 4-pyridyl859 —CH₂— pyridin-3,5-diyl CH₂CH₂ N-morpholinyl 860 —CH₂—pyridin-3,5-diyl CH₂CH₂ N-piperidinyl 861 —CH₂— pyridin-3,5-diyl —O—3-Me-2-pyridyl 862 —CH₂— pyridin-3,5-diyl —O— 4-Me-2-pyridyl 863 —CH₂—pyridin-3,5-diyl CH₂CH₂ 1-indolyl 864 —CH₂— pyridin-3,5-diyl —O—2-benzothienyl 865 —CH₂— pyridin-3,5-diyl —O— 2-benzofuranyl 866 —CH₂—pyridin-3,5-diyl CH₂CH₂ 1-benzimidazole 867 —CH₂— pyridin-3,5-diyl —O—2-naphthyl 868 —CH₂— pyridin-2,6-diyl —O— phenyl 869 —CH₂—pyridin-2,6-diyl —O— 3,3-diphenylmethyl 870 —CH₂— pyridin-2,6-diyl —O—2-F-phenyl 871 —CH₂— pyridin-2,6-diyl —O— 3-F-phenyl 872 —CH₂—pyridin-2,6-diyl —O— 4-F-phenyl 873 —CH₂— pyridin-2,6-diyl —O—2-Cl-phenyl 874 —CH₂— pyridin-2,6-diyl —O— 3-Cl-phenyl 875 —CH₂—pyridin-2,6-diyl —O— 4-Cl-phenyl 876 —CH₂— pyridin-2,6-diyl —O—2-Me-phenyl 877 —CH₂— pyridin-2,6-diyl —O— 3-Me-phenyl 878 —CH₂—pyridin-2,6-diyl —O— 4-Me-phenyl 879 —CH₂— pyridin-2,6-diyl —O—2-MeO-phenyl 880 —CH₂— pyridin-2,6-diyl —O— 3-MeO-phenyl 881 —CH₂—pyridin-2,6-diyl —O— 4-MeO-phenyl 882 —CH₂— pyridin-2,6-diyl —O—2-MeS-phenyl 883 —CH₂— pyridin-2,6-diyl —O— 3-MeS-phenyl 884 —CH₂—pyridin-2,6-diyl —O— 4-MeS-phenyl 885 —CH₂— pyridin-2,6-diyl —O—2-F₃C-phenyl 886 —CH₂— pyridin-2,6-diyl —O— 3-F₃C-phenyl 887 —CH₂—pyridin-2,6-diyl —O— 4-F₃C-phenyl 888 —CH₂— pyridin-2,6-diyl —O—2,3-diF-phenyl 889 —CH₂— pyridin-2,6-diyl —O— 2,4-diF-phenyl 890 —CH₂—pyridin-2,6-diyl —O— 2,5-diF-phenyl 891 —CH₂— pyridin-2,6-diyl —O—2,6-diF-phenyl 892 —CH₂— pyridin-2,6-diyl —O— 3,4-diF-phenyl 893 —CH₂—pyridin-2,6-diyl —O— 3,5-diF-phenyl 894 —CH₂— pyridin-2,6-diyl —O—2,3-diCl-phenyl 895 —CH₂— pyridin-2,6-diyl —O— 2,4-diCl-phenyl 896 —CH₂—pyridin-2,6-diyl —O— 2,5-diCl-phenyl 897 —CH₂— pyridin-2,6-diyl —O—2,6-diCl-phenyl 898 —CH₂— pyridin-2,6-diyl —O— 3,4-diCl-phenyl 899 —CH₂—pyridin-2,6-diyl —O— 3,5-diCl-phenyl 900 —CH₂— pyridin-2,6-diyl —O—2-Cl-3-F-phenyl 901 —CH₂— pyridin-2,6-diyl —O— 2-Cl-4-F-phenyl 902 —CH₂—pyridin-2,6-diyl —O— 2-Cl-5-F-phenyl 903 —CH₂— pyridin-2,6-diyl —O—3-Cl-4-F-phenyl 904 —CH₂— pyridin-2,6-diyl —O— 3-Cl-5-F-phenyl 905 —CH₂—pyridin-2,6-diyl —O— 4-Cl-2-F-phenyl 906 —CH₂— pyridin-2,6-diyl —O—4-Cl-3-F-phenyl 907 —CH₂— pyridin-2,6-diyl —O— 2,3-diMeO-phenyl 908—CH₂— pyridin-2,6-diyl —O— 2,4-diMeO-phenyl 909 —CH₂— pyridin-2,6-diyl—O— 2,5-diMeO-phenyl 910 —CH₂— pyridin-2,6-diyl —O— 2,6-diMeO-phenyl 911—CH₂— pyridin-2,6-diyl —O— 3,4-diMeO-phenyl 912 —CH₂— pyridin-2,6-diyl—O— 3,5-diMeO-phenyl 913 —CH₂— pyridin-2,6-diyl —O— cyclopropyl 914—CH₂— pyridin-2,6-diyl —O— cyclobutyl 915 —CH₂— pyridin-2,6-diyl —O—cyclopentyl 916 —CH₂— pyridin-2,6-diyl —O— cyclohexyl 917 —CH₂—pyridin-2,6-diyl —O— 2-furanyl 918 —CH₂— pyridin-2,6-diyl —O— 2-thienyl919 —CH₂— pyridin-2,6-diyl CH₂CH₂ 2-imidazolyl 920 —CH₂—pyridin-2,6-diyl —O— 2-pyridyl 921 —CH₂— pyridin-2,6-diyl —O— 3-pyridyl922 —CH₂— pyridin-2,6-diyl —O— 4-pyridyl 923 —CH₂— pyridin-2,6-diylCH₂CH₂ N-morpholinyl 924 —CH₂— pyridin-2,6-diyl CH₂CH₂ N-piperidinyl 925—CH₂— pyridin-2,6-diyl —O— 3-Me-2-pyridyl 926 —CH₂— pyridin-2,6-diyl —O—4-Me-2-pyridyl 927 —CH₂— pyridin-2,6-diyl CH₂CH₂ 1-indolyl 928 —CH₂—pyridin-2,6-diyl —O— 2-benzothienyl 929 —CH₂— pyridin-2,6-diyl —O—2-benzofuranyl 930 —CH₂— pyridin-2,6-diyl CH₂CH₂ 1-benzimidazole 931—CH₂— pyridin-2,6-diyl —O— 2-naphthyl 932 —CH₂— pyridin-2,4-diyl —O—phenyl 933 —CH₂— pyridin-2,4-diyl —O— 3,3-diphenylmethyl 934 —CH₂—pyridin-2,4-diyl —O— 2-F-phenyl 935 —CH₂— pyridin-2,4-diyl —O—3-F-phenyl 936 —CH₂— pyridin-2,4-diyl —O— 4-F-phenyl 937 —CH₂—pyridin-2,4-diyl —O— 2-Cl-phenyl 938 —CH₂— pyridin-2,4-diyl —O—3-Cl-phenyl 939 —CH₂— pyridin-2,4-diyl —O— 4-Cl-phenyl 940 —CH₂—pyridin-2,4-diyl —O— 2-Me-phenyl 941 —CH₂— pyridin-2,4-diyl —O—3-Me-phenyl 942 —CH₂— pyridin-2,4-diyl —O— 4-Me-phenyl 943 —CH₂—pyridin-2,4-diyl —O— 2-MeO-phenyl 944 —CH₂— pyridin-2,4-diyl —O—3-MeO-phenyl 945 —CH₂— pyridin-2,4-diyl —O— 4-MeO-phenyl 946 —CH₂—pyridin-2,4-diyl —O— 2-MeS-phenyl 947 —CH₂— pyridin-2,4-diyl —O—3-MeS-phenyl 948 —CH₂— pyridin-2,4-diyl —O— 4-MeS-phenyl 949 —CH₂—pyridin-2,4-diyl —O— 2-F₃C-phenyl 950 —CH₂— pyridin-2,4-diyl —O—3-F₃C-phenyl 951 —CH₂— pyridin-2,4-diyl —O— 4-F₃C-phenyl 952 —CH₂—pyridin-2,4-diyl —O— 2,3-diF-phenyl 953 —CH₂— pyridin-2,4-diyl —O—2,4-diF-phenyl 954 —CH₂— pyridin-2,4-diyl —O— 2,5-diF-phenyl 955 —CH₂—pyridin-2,4-diyl —O— 2,6-diF-phenyl 956 —CH₂— pyridin-2,4-diyl —O—3,4-diF-phenyl 957 —CH₂— pyridin-2,4-diyl —O— 3,5-diF-phenyl 958 —CH₂—pyridin-2,4-diyl —O— 2,3-diCl-phenyl 959 —CH₂— pyridin-2,4-diyl —O—2,4-diCl-phenyl 960 —CH₂— pyridin-2,4-diyl —O— 2,5-diCl-phenyl 961 —CH₂—pyridin-2,4-diyl —O— 2,6-diCl-phenyl 962 —CH₂— pyridin-2,4-diyl —O—3,4-diCl-phenyl 963 —CH₂— pyridin-2,4-diyl —O— 3,5-diCl-phenyl 964 —CH₂—pyridin-2,4-diyl —O— 2-Cl-3-F-phenyl 965 —CH₂— pyridin-2,4-diyl —O—2-Cl-4-F-phenyl 966 —CH₂— pyridin-2,4-diyl —O— 2-Cl-5-F-phenyl 967 —CH₂—pyridin-2,4-diyl —O— 3-Cl-4-F-phenyl 968 —CH₂— pyridin-2,4-diyl —O—3-Cl-5-F-phenyl 969 —CH₂— pyridin-2,4-diyl —O— 4-Cl-2-F-phenyl 970 —CH₂—pyridin-2,4-diyl —O— 4-Cl-3-F-phenyl 971 —CH₂— pyridin-2,4-diyl —O—2,3-diMeO-phenyl 972 —CH₂— pyridin-2,4-diyl —O— 2,4-diMeO-phenyl 973—CH₂— pyridin-2,4-diyl —O— 2,5-diMeO-phenyl 974 —CH₂— pyridin-2,4-diyl—O— 2,6-diMeO-phenyl 975 —CH₂— pyridin-2,4-diyl —O— 3,4-diMeO-phenyl 976—CH₂— pyridin-2,4-diyl —O— 3,5-diMeO-phenyl 977 —CH₂— pyridin-2,4-diyl—O— cyclopropyl 978 —CH₂— pyridin-2,4-diyl —O— cyclobutyl 979 —CH₂—pyridin-2,4-diyl —O— cyclopentyl 980 —CH₂— pyridin-2,4-diyl —O—cyclohexyl 981 —CH₂— pyridin-2,4-diyl —O— 2-furanyl 982 —CH₂—pyridin-2,4-diyl —O— 2-thienyl 983 —CH₂— pyridin-2,4-diyl —O—2-imidazolyl 984 —CH₂— pyridin-2,4-diyl —O— 2-pyridyl 985 —CH₂—pyridin-2,4-diyl —O— 3-pyridyl 986 —CH₂— pyridin-2,4-diyl —O— 4-pyridyl987 —CH₂— pyridin-2,4-diyl CH₂CH₂ N-morpholinyl 988 —CH₂—pyridin-2,4-diyl CH₂CH₂ N-piperidinyl 989 —CH₂— pyridin-2,4-diyl —O—3-Me-2-pyridyl 990 —CH₂— pyridin-2,4-diyl —O— 4-Me-2-pyridyl 991 —CH₂—pyridin-2,4-diyl CH₂CH₂ 1-indolyl 992 —CH₂— pyridin-2,4-diyl —O—2-benzothienyl 993 —CH₂— pyridin-2,4-diyl —O— 2-benzofuranyl 994 —CH₂—pyridin-2,4-diyl CH₂CH₂ 1-benzimidazole 995 —CH₂— pyridin-2,4-diyl —O—2-naphthyl 996 —CH₂— pyridin-4,2-diyl —O— phenyl 997 —CH₂—pyridin-4,2-diyl —O— 3,3-diphenylmethyl 998 —CH₂— pyridin-4,2-diyl —O—2-F-phenyl 999 —CH₂— pyridin-4,2-diyl —O— 3-F-phenyl 1000  —CH₂—pyridin-4,2-diyl —O— 4-F-phenyl 1001  —CH₂— pyridin-4,2-diyl —O—2-Cl-phenyl 1002  —CH₂— pyridin-4,2-diyl —O— 3-Cl-phenyl 1003  —CH₂—pyridin-4,2-diyl —O— 4-Cl-phenyl 1004  —CH₂— pyridin-4,2-diyl —O—2-Me-phenyl 1005  —CH₂— pyridin-4,2-diyl —O— 3-Me-phenyl 1006  —CH₂—pyridin-4,2-diyl —O— 4-Me-phenyl 1007  —CH₂— pyridin-4,2-diyl —O—2-MeO-phenyl 1008  —CH₂— pyridin-4,2-diyl —O— 3-MeO-phenyl 1009  —CH₂—pyridin-4,2-diyl —O— 4-MeO-phenyl 1010  —CH₂— pyridin-4,2-diyl —O—2-MeS-phenyl 1011  —CH₂— pyridin-4,2-diyl —O— 3-MeS-phenyl 1012  —CH₂—pyridin-4,2-diyl —O— 4-MeS-phenyl 1013  —CH₂— pyridin-4,2-diyl —O—2-F₃C-phenyl 1014  —CH₂— pyridin-4,2-diyl —O— 3-F₃C-phenyl 1015  —CH₂—pyridin-4,2-diyl —O— 4-F₃C-phenyl 1016  —CH₂— pyridin-4,2-diyl —O—2,3-diF-phenyl 1017  —CH₂— pyridin-4,2-diyl —O— 2,4-diF-phenyl 1018 —CH₂— pyridin-4,2-diyl —O— 2,5-diF-phenyl 1019  —CH₂— pyridin-4,2-diyl—O— 2,6-diF-phenyl 1020  —CH₂— pyridin-4,2-diyl —O— 3,4-diF-phenyl 1021 —CH₂— pyridin-4,2-diyl —O— 3,5-diF-phenyl 1022  —CH₂— pyridin-4,2-diyl—O— 2,3-diCl-phenyl 1023  —CH₂— pyridin-4,2-diyl —O— 2,4-diCl-phenyl1024  —CH₂— pyridin-4,2-diyl —O— 2,5-diCl-phenyl 1025  —CH₂—pyridin-4,2-diyl —O— 2,6-diCl-phenyl 1026  —CH₂— pyridin-4,2-diyl —O—3,4-diCl-phenyl 1027  —CH₂— pyridin-4,2-diyl —O— 3,5-diCl-phenyl 1028 —CH₂— pyridin-4,2-diyl —O— 2-Cl-3-F-phenyl 1029  —CH₂— pyridin-4,2-diyl—O— 2-Cl-4-F-phenyl 1030  —CH₂— pyridin-4,2-diyl —O— 2-Cl-5-F-phenyl1031  —CH₂— pyridin-4,2-diyl —O— 3-Cl-4-F-phenyl 1032  —CH₂—pyridin-4,2-diyl —O— 3-Cl-5-F-phenyl 1033  —CH₂— pyridin-4,2-diyl —O—4-Cl-2-F-phenyl 1034  —CH₂— pyridin-4,2-diyl —O— 4-Cl-3-F-phenyl 1035 —CH₂— pyridin-4,2-diyl —O— 2,3-diMeO-phenyl 1036  —CH₂— pyridin-4,2-diyl—O— 2,4-diMeO-phenyl 1037  —CH₂— pyridin-4,2-diyl —O— 2,5-diMeO-phenyl1038  —CH₂— pyridin-4,2-diyl —O— 2,6-diMeO-phenyl 1039  —CH₂—pyridin-4,2-diyl —O— 3,4-diMeO-phenyl 1040  —CH₂— pyridin-4,2-diyl —O—3,5-diMeO-phenyl 1041  —CH₂— pyridin-4,2-diyl —O— cyclopropyl 1042 —CH₂— pyridin-4,2-diyl —O— cyclobutyl 1043  —CH₂— pyridin-4,2-diyl —O—cyclopentyl 1044  —CH₂— pyridin-4,2-diyl —O— cyclohexyl 1045  —CH₂—pyridin-4,2-diyl —O— 2-furanyl 1046  —CH₂— pyridin-4,2-diyl —O—2-thienyl 1047  —CH₂— pyridin-4,2-diyl CH₂CH₂ 2-imidazolyl 1048  —CH₂—pyridin-4,2-diyl —O— 2-pyridyl 1049  —CH₂— pyridin-4,2-diyl —O—3-pyridyl 1050  —CH₂— pyridin-4,2-diyl —O— 4-pyridyl 1051  —CH₂—pyridin-4,2-diyl CH₂CH₂ N-morpholinyl 1052  —CH₂— pyridin-4,2-diylCH₂CH₂ N-piperidinyl 1053  —CH₂— pyridin-4,2-diyl —O— 3-Me-2-pyridyl1054  —CH₂— pyridin-4,2-diyl —O— 4-Me-2-pyridyl 1055  —CH₂—pyridin-4,2-diyl CH₂CH₂ 1-indolyl 1056  —CH₂— pyridin-4,2-diyl —O—2-benzothienyl 1057  —CH₂— pyridin-4,2-diyl —O— 2-benzofuranyl 1058 —CH₂— pyridin-4,2-diyl CH₂CH₂ 1-benzimidazole 1059  —CH₂—pyridin-4,2-diyl —O— 2-naphthyl 1060  —CH₂— piperidin-1,3-diyl —O—phenyl 1061  —CH₂— piperidin-1,3-diyl —O— 3,3-diphenylmethyl 1062  —CH₂—piperidin-1,3-diyl —O— 2-F-phenyl 1063  —CH₂— piperidin-1,3-diyl —O—3-F-phenyl 1064  —CH₂— piperidin-1,3-diyl —O— 4-F-phenyl 1065  —CH₂—piperidin-1,3-diyl —O— 2-Cl-phenyl 1066  —CH₂— piperidin-1,3-diyl —O—3-Cl-phenyl 1067  —CH₂— piperidin-1,3-diyl —O— 4-Cl-phenyl 1068  —CH₂—piperidin-1,3-diyl —O— 2-Me-phenyl 1069  —CH₂— piperidin-1,3-diyl —O—3-Me-phenyl 1070  —CH₂— piperidin-1,3-diyl —O— 4-Me-phenyl 1071  —CH₂—piperidin-1,3-diyl —O— 2-MeO-phenyl 1072  —CH₂— piperidin-1,3-diyl —O—3-MeO-phenyl 1073  —CH₂— piperidin-1,3-diyl —O— 4-MeO-phenyl 1074  —CH₂—piperidin-1,3-diyl —O— 2-MeS-phenyl 1075  —CH₂— piperidin-1,3-diyl —O—3-MeS-phenyl 1076  —CH₂— piperidin-1,3-diyl —O— 4-MeS-phenyl 1077  —CH₂—piperidin-1,3-diyl —O— 2-F₃C-phenyl 1078  —CH₂— piperidin-1,3-diyl —O—3-F₃C-phenyl 1079  —CH₂— piperidin-1,3-diyl —O— 4-F₃C-phenyl 1080  —CH₂—piperidin-1,3-diyl —O— 2,3-diF-phenyl 1081  —CH₂— piperidin-1,3-diyl —O—2,4-diF-phenyl 1082  —CH₂— piperidin-1,3-diyl —O— 2 5-diF-phenyl 1083 —CH₂— piperidin-1,3-diyl —O— 2,6-diF-phenyl 1084  —CH₂—piperidin-1,3-diyl —O— 3,4-diF-phenyl 1085  —CH₂— piperidin-1,3-diyl —O—3,5-diF-phenyl 1086  —CH₂— piperidin-1,3-diyl —O— 2,3-diCl-phenyl 1087 —CH₂— piperidin-1,3-diyl —O— 2,4-diCl-phenyl 1088  —CH₂—piperidin-1,3-diyl —O— 2,5-diCl-phenyl 1089  —CH₂— piperidin-1,3-diyl—O— 2,6-diCl-phenyl 1090  —CH₂— piperidin-1,3-diyl —O— 3,4-diCl-phenyl1091  —CH₂— piperidin-1,3-diyl —O— 3,5-diCl-phenyl 1092  —CH₂—piperidin-1,3-diyl —O— 2-Cl-3-F-phenyl 1093  —CH₂— piperidin-1,3-diyl—O— 2-Cl-4-F-phenyl 1094  —CH₂— piperidin-1,3-diyl —O— 2-Cl-5-F-phenyl1095  —CH₂— piperidin-1,3-diyl —O— 3-Cl-4-F-phenyl 1096  —CH₂—piperidin-1,3-diyl —O— 3-Cl-5-F-phenyl 1097  —CH₂— piperidin-1,3-diyl—O— 4-Cl-2-F-phenyl 1098  —CH₂— piperidin-1,3-diyl —O— 4-Cl-3-F-phenyl1099  —CH₂— piperidin-1,3-diyl —O— 2,3-diMeO-phenyl 1100  —CH₂—piperidin-1,3-diyl —O— 2,4-diMeO-phenyl 1101  —CH₂— piperidin-1,3-diyl—O— 2,5-diMeO-phenyl 1102  —CH₂— piperidin-1,3-diyl —O— 2,6-diMeO-phenyl1103  —CH₂— piperidin-1,3-diyl —O— 3,4-diMeO-phenyl 1104  —CH₂—piperidin-1,3-diyl —O— 3,5-diMeO-phenyl 1105  —CH₂— piperidin-1,3-diyl—O— cyclopropyl 1106  —CH₂— piperidin-1,3-diyl —O— cyclobutyl 1107 —CH₂— piperidin-1,3-diyl —O— cyclopentyl 1108  —CH₂— piperidin-1,3-diyl—O— cyclohexyl 1109  —CH₂— piperidin-1,3-diyl —O— 2-furanyl 1110  —CH₂—piperidin-1,3-diyl —O— 2-thienyl 1111  —CH₂— piperidin-1,3-diyl CH₂CH₂2-imidazolyl 1112  —CH₂— piperidin-1,3-diyl —O— 2-pyridyl 1113  —CH₂—piperidin-1,3-diyl —O— 3-pyridyl 1114  —CH₂— piperidin-1,3-diyl —O—4-pyridyl 1115  —CH₂— piperidin-1,3-diyl CH₂CH₂ N-morpholinyl 1116 —CH₂— piperidin-1,3-diyl CH₂CH₂ N-piperidinyl 1117  —CH₂—piperidin-1,3-diyl —O— 3-Me-2-pyridyl 1118  —CH₂— piperidin-1,3-diyl —O—4-Me-2-pyridyl 1119  —CH₂— piperidin-1,3-diyl CH₂CH₂ 1-indolyl 1120 —CH₂— piperidin-1,3-diyl —O— 2-benzothienyl 1121  —CH₂—piperidin-1,3-diyl —O— 2-benzofuranyl 1122  —CH₂— piperidin-1,3-diylCH₂CH₂ 1-benzimidazole 1123  —CH₂— piperidin-1,3-diyl —O— 2-naphthyl1124  —CH₂— piperidin-3,1-diyl —O— Phenyl 1125  —CH₂— piperidin-3,1-diyl—O— 3,3-diphenylmethyl 1126  —CH₂— piperidin-3,1-diyl —O— 2-F-phenyl1127  —CH₂— piperidin-3,1-diyl —O— 3-F-phenyl 1128  —CH₂—piperidin-3,1-diyl —O— 4-F-phenyl 1129  —CH₂— piperidin-3,1-diyl —O—2-Cl-phenyl 1130  —CH₂— piperidin-3,1-diyl —O— 3-Cl-phenyl 1131  —CH₂—piperidin-3,1-diyl —O— 4-Cl-phenyl 1132  —CH₂— piperidin-3,1-diyl —O—2-Me-phenyl 1133  —CH₂— piperidin-3,1-diyl —O— 3-Me-phenyl 1134  —CH₂—piperidin-3,1-diyl —O— 4-Me-phenyl 1135  —CH₂— piperidin-3,1-diyl —O—2-MeO-phenyl 1136  —CH₂— piperidin-3,1-diyl —O— 3-MeO-phenyl 1137  —CH₂—piperidin-3,1-diyl —O— 4-MeO-phenyl 1138  —CH₂— piperidin-3,1-diyl —O—2-MeS-phenyl 1139  —CH₂— piperidin-3,1-diyl —O— 3-MeS-phenyl 1140  —CH₂—piperidin-3,1-diyl —O— 4-MeS-phenyl 1141  —CH₂— piperidin-3,1-diyl —O—2-F₃C-phenyl 1142  —CH₂— piperidin-3,1-diyl —O— 3-F₃C-phenyl 1143  —CH₂—piperidin-3,1-diyl —O— 4-F₃C-phenyl 1144  —CH₂— piperidin-3,1-diyl —O—2,3-diF-phenyl 1145  —CH₂— piperidin-3,1-diyl —O— 2,4-diF-phenyl 1146 —CH₂— piperidin-3,1-diyl —O— 2,5-diF-phenyl 1147  —CH₂—piperidin-3,1-diyl —O— 2,6-diF-phenyl 1148  —CH₂— piperidin-3,1-diyl —O—3,4-diF-phenyl 1149  —CH₂— piperidin-3,1-diyl —O— 3,5-diF-phenyl 1150 —CH₂— piperidin-3,1-diyl —O— 2,3-diCl-phenyl 1151  —CH₂—piperidin-3,1-diyl —O— 2,4-diCl-phenyl 1152  —CH₂— piperidin-3,1-diyl—O— 2,5-diCl-phenyl 1153  —CH₂— piperidin-3,1-diyl —O— 2,6-diCl-phenyl1154  —CH₂— piperidin-3,1-diyl —O— 3 4-diCl-phenyl 1155  —CH₂—piperidin-3,1-diyl —O— 3,5-diCl-phenyl 1156  —CH₂— piperidin-3,1-diyl—O— 2-Cl-3-F-phenyl 1157  —CH₂— piperidin-3,1-diyl —O— 2-Cl-4-F-phenyl1158  —CH₂— piperidin-3,1-diyl —O— 2-Cl-5-F-phenyl 1159  —CH₂—piperidin-3,1-diyl —O— 3-Cl-4-F-phenyl 1160  —CH₂— piperidin-3,1-diyl—O— 3-Cl-5-F-phenyl 1161  —CH₂— piperidin-3,1-diyl —O— 4-Cl-2-F-phenyl1162  —CH₂— piperidin-3,1-diyl —O— 4-Cl-3-F-phenyl 1163  —CH₂—piperidin-3,1-diyl —O— 2,3-diMeO-phenyl 1164  —CH₂— piperidin-3,1-diyl—O— 2,4-diMeO-phenyl 1165  —CH₂— piperidin-3,1-diyl —O— 2,5-diMeO-phenyl1166  —CH₂— piperidin-3,1-diyl —O— 2,6-diMeO-phenyl 1167  —CH₂—piperidin-3,1-diyl —O— 3,4-diMeO-phenyl 1168  —CH₂— piperidin-3,1-diyl—O— 3,5-diMeO-phenyl 1169  —CH₂— piperidin-3,1-diyl —O— Cyclopropyl1170  —CH₂— piperidin-3,1-diyl —O— Cyclobutyl 1171  —CH₂—piperidin-3,1-diyl —O— Cyclopentyl 1172  —CH₂— piperidin-3,1-diyl —O—Cyclohexyl 1173  —CH₂— piperidin-3,1-diyl —O— 2-furanyl 1174  —CH₂—piperidin-3,1-diyl —O— 2-thienyl 1175  —CH₂— piperidin-3,1-diyl CH₂CH₂2-imidazolyl 1176  —CH₂— piperidin-3,1-diyl —O— 2-pyridyl 1177  —CH₂—piperidin-3,1-diyl —O— 3-pyridyl 1178  —CH₂— piperidin-3,1-diyl —O—4-pyridyl 1179  —CH₂— piperidin-3,1-diyl CH₂CH₂ N-morpholinyl 1180 —CH₂— piperidin-3,1-diyl CH₂CH₂ N-piperidinyl 1181  —CH₂—piperidin-3,1-diyl —O— 3-Me-2-pyridyl 1182  —CH₂— piperidin-3,1-diyl —O—4-Me-2-pyridyl 1183  —CH₂— piperidin-3,1-diyl CH₂CH₂ 1-indolyl 1184 —CH₂— piperidin-3,1-diyl —O— 2-benzothienyl 1185  —CH₂—piperidin-3,1-diyl —O— 2-benzofuranyl 1186  —CH₂— piperidin-3,1-diylCH₂CH₂ 1-benzimidazole 1187  —CH₂— piperidin-3,1-diyl —O— 2-naphthyl1188  —CH₂— Cyclohex-1,3-diyl —O— Phenyl 1189  —CH₂— Cyclohex-1,3-diyl—O— 3,3-diphenylmethyl 1190  —CH₂— Cyclohex-1,3-diyl —O— 2-F-phenyl1191  —CH₂— Cyclohex-1,3-diyl —O— 3-F-phenyl 1192  —CH₂—Cyclohex-1,3-diyl —O— 4-F-phenyl 1193  —CH₂— Cyclohex-1,3-diyl —O—2-Cl-phenyl 1194  —CH₂— Cyclohex-1,3-diyl —O— 3-Cl-phenyl 1195  —CH₂—Cyclohex-1,3-diyl —O— 4-Cl-phenyl 1196  —CH₂— Cyclohex-1,3-diyl —O—2-Me-phenyl 1197  —CH₂— Cyclohex-1,3-diyl —O— 3-Me-phenyl 1198  —CH₂—Cyclohex-1,3-diyl —O— 4-Me-phenyl 1199  —CH₂— Cyclohex-1,3-diyl —O—2-MeO-phenyl 1200  —CH₂— Cyclohex-1,3-diyl —O— 3-MeO-phenyl 1201  —CH₂—Cyclohex-1,3-diyl —O— 4-MeO-phenyl 1202  —CH₂— Cyclohex-1,3-diyl —O—2-MeS-phenyl 1203  —CH₂— Cyclohex-1,3-diyl —O— 3-MeS-phenyl 1204  —CH₂—Cyclohex-1,3-diyl —O— 4-MeS-phenyl 1205  —CH₂— Cyclohex-1,3-diyl —O—2-F₃C-phenyl 1206  —CH₂— Cyclohex-1,3-diyl —O— 3-F₃C-phenyl 1207  —CH₂—Cyclohex-1,3-diyl —O— 4-F₃C-phenyl 1208  —CH₂— Cyclohex-1,3-diyl —O—2,3-diF-phenyl 1209  —CH₂— Cyclohex-1,3-diyl —O— 2,4-diF-phenyl 1210 —CH₂— Cyclohex-1,3-diyl —O— 2,5-diF-phenyl 1211  —CH₂— Cyclohex-1,3-diyl—O— 2,6-diF-phenyl 1212  —CH₂— Cyclohex-1,3-diyl —O— 3,4-diF-phenyl1213  —CH₂— Cyclohex-1,3-diyl —O— 3,5-diF-phenyl 1214  —CH₂—Cyclohex-1,3-diyl —O— 2,3-diCl-phenyl 1215  —CH₂— Cyclohex-1,3-diyl —O—2,4-diCl-phenyl 1216  —CH₂— Cyclohex-1,3-diyl —O— 2,5-diCl-phenyl 1217 —CH₂— Cyclohex-1,3-diyl —O— 2,6-diCl-phenyl 1218  —CH₂—Cyclohex-1,3-diyl —O— 3,4-diCl-phenyl 1219  —CH₂— Cyclohex-1,3-diyl —O—3,5-diCl-phenyl 1220  —CH₂— Cyclohex-1,3-diyl —O— 2-Cl-3-F-phenyl 1221 —CH₂— Cyclohex-1,3-diyl —O— 2-Cl-4-F-phenyl 1222  —CH₂—Cyclohex-1,3-diyl —O— 2-Cl-5-F-phenyl 1223  —CH₂— Cyclohex-1,3-diyl —O—3-Cl-4-F-phenyl 1224  —CH₂— Cyclohex-1,3-diyl —O— 3-Cl-5-F-phenyl 1225 —CH₂— Cyclohex-1,3-diyl —O— 4-Cl-2-F-phenyl 1226  —CH₂—Cyclohex-1,3-diyl —O— 4-Cl-3-F-phenyl 1227  —CH₂— Cyclohex-1,3-diyl —O—2,3-diMeO-phenyl 1228  —CH₂— Cyclohex-1,3-diyl —O— 2,4-diMeO-phenyl1229  —CH₂— Cyclohex-1,3-diyl —O— 2,5-diMeO-phenyl 1230  —CH₂—Cyclohex-1,3-diyl —O— 2,6-diMeO-phenyl 1231  —CH₂— Cyclohex-1,3-diyl —O—3,4-diMeO-phenyl 1232  —CH₂— Cyclohex-1,3-diyl —O— 3,5-diMeO-phenyl1233  —CH₂— Cyclohex-1,3-diyl —O— Cyclopropyl 1234  —CH₂—Cyclohex-1,3-diyl —O— Cyclobutyl 1235  —CH₂— Cyclohex-1,3-diyl —O—Cyclopentyl 1236  —CH₂— Cyclohex-1,3-diyl —O— Cyclohexyl 1237  —CH₂—Cyclohex-1,3-diyl —O— 2-furanyl 1238  —CH₂— Cyclohex-1,3-diyl —O—2-thienyl 1239  —CH₂— Cyclohex-1,3-diyl CH₂CH₂ 2-imidazolyl 1240  —CH₂—Cyclohex-1,3-diyl —O— 2-pyridyl 1241  —CH₂— Cyclohex-1,3-diyl —O—3-pyridyl 1242  —CH₂— Cyclohex-1,3-diyl —O— 4-pyridyl 1243  —CH₂—Cyclohex-1,3-diyl CH₂CH₂ N-morpholinyl 1244  —CH₂— Cyclohex-1,3-diylCH₂CH₂ N-piperidinyl 1245  —CH₂— Cyclohex-1,3-diyl —O— 3-Me-2-pyridyl1246  —CH₂— Cyclohex-1,3-diyl —O— 4-Me-2-pyridyl 1247  —CH₂—Cyclohex-1,3-diyl CH₂CH₂ 1-indolyl 1248  —CH₂— Cyclohex-1,3-diyl —O—2-benzothienyl 1249  —CH₂— Cyclohex-1,3-diyl —O— 2-benzofuranyl 1250 —CH₂— Cyclohex-1,3-diyl CH₂CH₂ 1-benzimidazole 1251  —CH₂—Cyclohex-1,3-diyl —O— 2-naphthyl 1252  —CH₂— Cyclopropan-1,2-diyl —O—Phenyl 1253  —CH₂— Cyclopropan-1,2-diyl —O— 3.3-diphenylmethyl 1254 —CH₂— cyclopropan-1,2-diyl —O— 2-F-phenyl 1255  —CH₂—cyclopropan-1,2-diyl —O— 3-F-phenyl 1256  —CH₂— cyclopropan-1,2-diyl —O—4-F-phenyl 1257  —CH₂— cyclopropan-1,2-diyl —O— 2-Cl-phenyl 1258  —CH₂—cyclopropan-1,2-diyl —O— 3-Cl-phenyl 1259  —CH₂— cyclopropan-1,2-diyl—O— 4-Cl-phenyl 1260  —CH₂— cyclopropan-1,2-diyl —O— 2-Me-phenyl 1261 —CH₂— cyclopropan-1,2-diyl —O— 3-Me-phenyl 1262  —CH₂—cyclopropan-1,2-diyl —O— 4-Me-phenyl 1263  —CH₂— cyclopropan-1,2-diyl—O— 2-MeO-phenyl 1264  —CH₂— cyclopropan-1,2-diyl —O— 3-MeO-phenyl 1265 —CH₂— cyclopropan-1,2-diyl —O— 4-MeO-phenyl 1266  —CH₂—cyclopropan-1,2-diyl —O— 2-MeS-phenyl 1267  —CH₂— cyclopropan-1,2-diyl—O— 3-MeS-phenyl 1268  —CH₂— cyclopropan-1,2-diyl —O— 4-MeS-phenyl 1269 —CH₂— cyclopropan-1,2-diyl —O— 2-F₃C-phenyl 1270  —CH₂—cyclopropan-1,2-diyl —O— 3-F₃C-phenyl 1271  —CH₂— cyclopropan-1,2-diyl—O— 4-F₃C-phenyl 1272  —CH₂— cyclopropan-1,2-diyl —O— 2,3-diF-phenyl1273  —CH₂— cyclopropan-1,2-diyl —O— 2,4-diF-phenyl 1274  —CH₂—cyclopropan-1,2-diyl —O— 2,5-diF-phenyl 1275  —CH₂— cyclopropan-1,2-diyl—O— 2,6-diF-phenyl 1276  —CH₂— cyclopropan-1,2-diyl —O— 3,4-diF-phenyl1277  —CH₂— cyclopropan-1,2-diyl —O— 3,5-diF-phenyl 1278  —CH₂—cyclopropan-1,2-diyl —O— 2,3-diCl-phenyl 1279  —CH₂—cyclopropan-1,2-diyl —O— 2,4-diCl-phenyl 1280  —CH₂—cyclopropan-1,2-diyl —O— 2,5-diCl-phenyl 1281  —CH₂—cyclopropan-1,2-diyl —O— 2,6-diCl-phenyl 1282  —CH₂—cyclopropan-1,2-diyl —O— 3,4-diCl-phenyl 1283  —CH₂—cyclopropan-1,2-diyl —O— 3,5-diCl-phenyl 1284  —CH₂—cyclopropan-1,2-diyl —O— 2-Cl-3-F-phenyl 1285  —CH₂—cyclopropan-1,2-diyl —O— 2-Cl-4-F-phenyl 1286  —CH₂—cyclopropan-1,2-diyl —O— 2-Cl-5-F-phenyl 1287  —CH₂—cyclopropan-1,2-diyl —O— 3-Cl-4-F-phenyl 1288  —CH₂—cyclopropan-1,2-diyl —O— 3-Cl-5-F-phenyl 1289  —CH₂—cyclopropan-1,2-diyl —O— 4-Cl-2-F-phenyl 1290  —CH₂—cyclopropan-1,2-diyl —O— 4-Cl-3-F-phenyl 1291  —CH₂—cyclopropan-1,2-diyl —O— 2,3-diMeO-phenyl 1292  —CH₂—cyclopropan-1,2-diyl —O— 2,4-diMeO-phenyl 1293  —CH₂—cyclopropan-1,2-diyl —O— 2,5-diMeO-phenyl 1294  —CH₂—cyclopropan-1,2-diyl —O— 2,6-diMeO-phenyl 1295  —CH₂—cyclopropan-1,2-diyl —O— 3,4-diMeO-phenyl 1296  —CH₂—cyclopropan-1,2-diyl —O— 3,5-diMeO-phenyl 1297  —CH₂—cyclopropan-1,2-diyl —O— Cyclopropyl 1298  —CH₂— cyclopropan-1,2-diyl—O— Cyclobutyl 1299  —CH₂— cyclopropan-1,2-diyl —O— Cyclopentyl 1300 —CH₂— cyclopropan-1,2-diyl —O— Cyclohexyl 1301  —CH₂—cyclopropan-1,2-diyl —O— 2-furanyl 1302  —CH₂— cyclopropan-1,2-diyl —O—2-thienyl 1303  —CH₂— cyclopropan-1,2-diyl CH₂CH₂ 2-imidazolyl 1304 —CH₂— cyclopropan-1,2-diyl —O— 2-pyridyl 1305  —CH₂—cyclopropan-1,2-diyl —O— 3-pyridyl 1306  —CH₂— cyclopropan-1,2-diyl —O—4-pyridyl 1307  —CH₂— cyclopropan-1,2-diyl CH₂CH₂ N-morpholinyl 1308 —CH₂— cyclopropan-1,2-diyl CH₂CH₂ N-piperidinyl 1309  —CH₂—cyclopropan-1,2-diyl —O— 3-Me-2-pyridyl 1310  —CH₂— cyclopropan-1,2-diyl—O— 4-Me-2-pyridyl 1311  —CH₂— cyclopropan-1,2-diyl CH₂CH₂ 1-indolyl1312  —CH₂— cyclopropan-1,2-diyl —O— 2-benzothienyl 1313  —CH₂—cyclopropan-1,2-diyl —O— 2-benzofuranyl 1314  —CH₂— cyclopropan-1,2-diylCH₂CH₂ 1-benzimidazole 1315  —CH₂— cyclopropan-1,2-diyl —O— 2-naphthyl1316  —CH₂— cyclopentan-1,3-diyl —O— Phenyl 1317  —CH₂—cyclopentan-1,3-diyl —O— 3,3-diphenylmethyl 1318  —CH₂—cyclopentan-1,3-diyl —O— 2-F-phenyl 1319  —CH₂— cyclopentan-1,3-diyl —O—3-F-phenyl 1320  —CH₂— cyclopentan-1,3-diyl —O— 4-F-phenyl 1321  —CH₂—cyclopentan-1,3-diyl —O— 2-Cl-phenyl 1322  —CH₂— cyclopentan-1,3-diyl—O— 3-Cl-phenyl 1323  —CH₂— cyclopentan-1,3-diyl —O— 4-Cl-phenyl 1324 —CH₂— cyclopentan-1,3-diyl —O— 2-Me-phenyl 1325  —CH₂—cyclopentan-1,3-diyl —O— 3-Me-phenyl 1326  —CH₂— cyclopentan-1,3-diyl—O— 4-Me-phenyl 1327  —CH₂— cyclopentan-1,3-diyl —O— 2-MeO-phenyl 1328 —CH₂— cyclopentan-1,3-diyl —O— 3-MeO-phenyl 1329  —CH₂—cyclopentan-1,3-diyl —O— 4-MeO-phenyl 1330  —CH₂— cyclopentan-1,3-diyl—O— 2-MeS-phenyl 1331  —CH₂— cyclopentan-1,3-diyl —O— 3-MeS-phenyl 1332 —CH₂— cyclopentan-1,3-diyl —O— 4-MeS-phenyl 1333  —CH₂—cyclopentan-1,3-diyl —O— 2-F₃C-phenyl 1334  —CH₂— cyclopentan-1,3-diyl—O— 3-F₃C-phenyl 1335  —CH₂— cyclopentan-1,3-diyl —O— 4-F₃C-phenyl 1336 —CH₂— cyclopentan-1,3-diyl —O— 2,3-diF-phenyl 1337  —CH₂—cyclopentan-1,3-diyl —O— 2,4-diF-phenyl 1338  —CH₂— cyclopentan-1,3-diyl—O— 2,5-diF-phenyl 1339  —CH₂— cyclopentan-1,3-diyl —O— 2,6-diF-phenyl1340  —CH₂— cyclopentan-1,3-diyl —O— 3,4-diF-phenyl 1341  —CH₂—cyclopentan-1,3-diyl —O— 3,5-diF-phenyl 1342  —CH₂— cyclopentan-1,3-diyl—O— 2,3-diCl-phenyl 1343  —CH₂— cyclopentan-1,3-diyl —O— 2,4-diCl-phenyl1344  —CH₂— cyclopentan-1,3-diyl —O— 2,5-diCl-phenyl 1345  —CH₂—cyclopentan-1,3-diyl —O— 2,6-diCl-phenyl 1346  —CH₂—cyclopentan-1,3-diyl —O— 3,4-diCl-phenyl 1347  —CH₂—cyclopentan-1,3-diyl —O— 3,5-diCl-phenyl 1348  —CH₂—cyclopentan-1,3-diyl —O— 2-Cl-3-F-phenyl 1349  —CH₂—cyclopentan-1,3-diyl —O— 2-Cl-4-F-phenyl 1350  —CH₂—cyclopentan-1,3-diyl —O— 2-Cl-5-F-phenyl 1351  —CH₂—cyclopentan-1,3-diyl —O— 3-Cl-4-F-phenyl 1352  —CH₂—cyclopentan-1,3-diyl —O— 3-Cl-5-F-phenyl 1353  —CH₂—cyclopentan-1,3-diyl —O— 4-Cl-2-F-phenyl 1354  —CH₂—cyclopentan-1,3-diyl —O— 4-Cl-3-F-phenyl 1355  —CH₂—cyclopentan-1,3-diyl —O— 2,3-diMeO-phenyl 1356  —CH₂—cyclopentan-1,3-diyl —O— 2,4-diMeO-phenyl 1357  —CH₂—cyclopentan-1,3-diyl —O— 2,5-diMeO-phenyl 1358  —CH₂—cyclopentan-1,3-diyl —O— 2,6-diMeO-phenyl 1359  —CH₂—cyclopentan-1,3-diyl —O— 3,4-diMeO-phenyl 1360  —CH₂—cyclopentan-1,3-diyl —O— 3,5-diMeO-phenyl 1361  —CH₂—cyclopentan-1,3-diyl —O— Cyclopropyl 1362  —CH₂— cyclopentan-1,3-diyl—O— Cyclobutyl 1363  —CH₂— cyclopentan-1,3-diyl —O— Cyclopentyl 1364 —CH₂— cyclopentan-1,3-diyl —O— Cyclohexyl 1365  —CH₂—cyclopentan-1,3-diyl —O— 2-furanyl 1366  —CH₂— cyclopentan-1,3-diyl —O—2-thienyl 1367  —CH₂— cyclopentan-1,3-diyl CH₂CH₂ 2-imidazolyl 1368 —CH₂— cyclopentan-1,3-diyl —O— 2-pyridyl 1369  —CH₂—cyclopentan-1,3-diyl —O— 3-pyridyl 1370  —CH₂— cyclopentan-1,3-diyl —O—4-pyridyl 1371  —CH₂— cyclopentan-1,3-diyl CH₂CH₂ N-morpholinyl 1372 —CH₂— cyclopentan-1,3-diyl CH₂CH₂ N-piperidinyl 1373  —CH₂—cyclopentan-1,3-diyl —O— 3-Me-2-pyridyl 1374  —CH₂— cyclopentan-1,3-diyl—O— 4-Me-2-pyridyl 1375  —CH₂— cyclopentan-1,3-diyl CH₂CH₂ 1-indolyl1376  —CH₂— cyclopentan-1,3-diyl —O— 2-benzothienyl 1377  —CH₂—cyclopentan-1,3-diyl —O— 2-benzofuranyl 1378  —CH₂— cyclopentan-1,3-diylCH₂CH₂ 1-benzimidazole 1379  —CH₂— cyclopentan-1,3-diyl —O— 2-naphthyl1380  —CH₂— bond bond phenyl 1381  —CH₂— bond bond 3,3-diphenyl 1382 —CH₂— bond bond 2-F-phenyl 1383  —CH₂— bond bond 3-F-phenyl 1384  —CH₂—bond bond 4-F-phenyl 1385  —CH₂— bond bond 2-Cl-phenyl 1386  —CH₂— bondbond 3-Cl-phenyl 1387  —CH₂— bond bond 4-Cl-phenyl 1388  —CH₂— bond bond2-Me-phenyl 1389  —CH₂— bond bond 3-Me-phenyl 1390  —CH₂— bond bond4-Me-phenyl 1391  —CH₂— bond bond 2-MeO-phenyl 1392  —CH₂— bond bond3-MeO-phenyl 1393  —CH₂— bond bond 4-MeO-phenyl 1394  —CH₂— bond bond2-MeS-phenyl 1395  —CH₂— bond bond 3-MeS-phenyl 1396  —CH₂— bond bond4-MeS-phenyl 1397  —CH₂— bond bond 2-F₃C-phenyl 1398  —CH₂— bond bond3-F₃C-phenyl 1399  —CH₂— bond bond 4-F₃C-phenyl 1400  —CH₂— bond bond2,3-diF-phenyl 1401  —CH₂— bond bond 2,4-diF-phenyl 1402  —CH₂— bondbond 2,5-diF-phenyl 1403  —CH₂— bond bond 2,6-diF-phenyl 1404  —CH₂—bond bond 3,4-diF-phenyl 1405  —CH₂— bond bond 3,5-diF-phenyl 1406 —CH₂— bond bond 2,3-diCl-phenyl 1407  —CH₂— bond bond 2,4-diCl-phenyl1408  —CH₂— bond bond 2,5-diCl-phenyl 1409  —CH₂— bond bond2,6-diCl-phenyl 1410  —CH₂— bond bond 3,4-diCl-phenyl 1411  —CH₂— bondbond 3,5-diCl-phenyl 1412  —CH₂— bond bond 2-Cl-3-F-phenyl 1413  —CH₂—bond bond 2-Cl-4-F-phenyl 1414  —CH₂— bond bond 2-Cl-5-F-phenyl 1415 —CH₂— bond bond 3-Cl-4-F-phenyl 1416  —CH₂— bond bond 3-Cl-5-F-phenyl1417  —CH₂— bond bond 4-Cl-2-F-phenyl 1418  —CH₂— bond bond4-Cl-3-F-phenyl 1419  —CH₂— bond bond 2,3-diMeO-phenyl 1420  —CH₂— bondbond 2,4-diMeO-phenyl 1421  —CH₂— bond bond 2,5-diMeO-phenyl 1422  —CH₂—bond bond 2,6-diMeO-phenyl 1423  —CH₂— bond bond 3,4-diMeO-phenyl 1424 —CH₂— bond bond 3,5-diMeO-phenyl 1425  —CH₂— bond bond cyclopropyl 1426 —CH₂— bond bond cyclobutyl 1427  —CH₂— bond bond cyclopentyl 1428  —CH₂—bond bond cyclohexyl 1429  —CH₂— bond bond 2-furanyl 1430  —CH₂— bondbond 2-thienyl 1431  —CH₂— bond bond 2-imidazolyl 1432  —CH₂— bond bond2-pyridyl 1433  —CH₂— bond bond 3-pyridyl 1434  —CH₂— bond bond4-pyridyl 1435  —CH₂— bond bond N-morpholinyl 1436  —CH₂— bond bondN-piperidinyl 1437  —CH₂— bond bond 3-Me-2-pyridyl 1438  —CH₂— bond bond4-Me-2-pyridyl 1439  —CH₂— bond bond 1-indolyl 1440  —CH₂— bond bond2-benzothienyl 1441  —CH₂— bond bond 2-benzofuranyl 1442  —CH₂— bondbond 1-benzimidazole 1443  —CH₂— bond bond 2-naphthyl 1444  —CH₂CH₂—bond bond phenyl 1445  —CH₂CH₂— bond bond 3,3-diphenyl 1446  —CH₂CH₂—bond bond 2-F-phenyl 1447  —CH₂CH₂— bond bond 3-F-phenyl 1448  —CH₂CH₂—bond bond 4-F-phenyl 1449  —CH₂CH₂— bond bond 2-Cl-phenyl 1450  —CH₂CH₂—bond bond 3-Cl-phenyl 1451  —CH₂CH₂— bond bond 4-Cl-phenyl 1452 —CH₂CH₂— bond bond 2-Me-phenyl 1453  —CH₂CH₂— bond bond 3-Me-phenyl1454  —CH₂CH₂— bond bond 4-Me-phenyl 1455  —CH₂CH₂— bond bond2-MeO-phenyl 1456  —CH₂CH₂— bond bond 3-MeO-phenyl 1457  —CH₂CH₂— bondbond 4-MeO-phenyl 1458  —CH₂CH₂— bond bond 2-MeS-phenyl 1459  —CH₂CH₂—bond bond 3-MeS-phenyl 1460  —CH₂CH₂— bond bond 4-MeS-phenyl 1461 —CH₂CH₂— bond bond 2-F₃C-phenyl 1462  —CH₂CH₂— bond bond 3-F₃C-phenyl1463  —CH₂CH₂— bond bond 4-F₃C-phenyl 1464  —CH₂CH₂— bond bond2,3-diF-phenyl 1465  —CH₂CH₂— bond bond 2,4-diF-phenyl 1466  —CH₂CH₂—bond bond 2,5-diF-phenyl 1467  —CH₂CH₂— bond bond 2,6-diF-phenyl 1468 —CH₂CH₂— bond bond 3,4-diF-phenyl 1469  —CH₂CH₂— bond bond3,5-diF-phenyl 1470  —CH₂CH₂— bond bond 2,3-diCl-phenyl 1471  —CH₂CH₂—bond bond 2,4-diCl-phenyl 1472  —CH₂CH₂— bond bond 2,5-diCl-phenyl 1473 —CH₂CH₂— bond bond 2,6-diCl-phenyl 1474  —CH₂CH₂— bond bond3,4-diCl-phenyl 1475  —CH₂CH₂— bond bond 3,5-diCl-phenyl 1476  —CH₂CH₂—bond bond 2-Cl-3-F-phenyl 1477  —CH₂CH₂— bond bond 2-Cl-4-F-phenyl 1478 —CH₂CH₂— bond bond 2-Cl-5-F-phenyl 1479  —CH₂CH₂— bond bond3-Cl-4-F-phenyl 1480  —CH₂CH₂— bond bond 3-Cl-5-F-phenyl 1481  —CH₂CH₂—bond bond 4-Cl-2-F-phenyl 1482  —CH₂CH₂— bond bond 4-Cl-3-F-phenyl 1483 —CH₂CH₂— bond bond 2,3-diMeO-phenyl 1484  —CH₂CH₂— bond bond2,4-diMeO-phenyl 1485  —CH₂CH₂— bond bond 2,5-diMeO-phenyl 1486 —CH₂CH₂— bond bond 2,6-diMeO-phenyl 1487  —CH₂CH₂— bond bond3,4-diMeO-phenyl 1488  —CH₂CH₂— bond bond 3,5-diMeO-phenyl 1489 —CH₂CH₂— bond bond cyclopropyl 1490  —CH₂CH₂— bond bond cyclobutyl 1491 —CH₂CH₂— bond bond cyclopentyl 1492  —CH₂CH₂— bond bond cyclohexyl 1493 —CH₂CH₂— bond bond 2-furanyl 1494  —CH₂CH₂— bond bond 2-thienyl 1495 —CH₂CH₂— bond bond 2-imidazolyl 1496  —CH₂CH₂— bond bond 2-pyridyl 1497 —CH₂CH₂— bond bond 3-pyridyl 1498  —CH₂CH₂— bond bond 4-pyridyl 1499 —CH₂CH₂— bond bond N-morpholinyl 1500  —CH₂CH₂— bond bond N-piperidinyl1501  —CH₂CH₂— bond bond 3-Me-2-pyridyl 1502  —CH₂CH₂— bond bond4-Me-2-pyridyl 1503  —CH₂CH₂— bond bond 1-indolyl 1504  —CH₂CH₂— bondbond 2-benzothienyl 1505  —CH₂CH₂— bond bond 2-benzofuranyl 1506 —CH₂CH₂— bond bond 1-benzimidazole 1507  —CH₂CH₂— bond bond 2-naphthyl1508  —CH₂CH₂CH₂— bond bond phenyl 1509  —CH₂CH₂CH₂— bond bond3,3-diphenyl 1510  —CH₂CH₂CH₂— bond bond 2-F-phenyl 1511  —CH₂CH₂CH₂—bond bond 3-F-phenyl 1512  —CH₂CH₂CH₂— bond bond 4-F-phenyl 1513 —CH₂CH₂CH₂— bond bond 2-Cl-phenyl 1514  —CH₂CH₂CH₂— bond bond3-Cl-phenyl 1515  —CH₂CH₂CH₂— bond bond 4-Cl-phenyl 1516  —CH₂CH₂CH₂—bond bond 2-Me-phenyl 1517  —CH₂CH₂CH₂— bond bond 3-Me-phenyl 1518 —CH₂CH₂CH₂— bond bond 4-Me-phenyl 1519  —CH₂CH₂CH₂— bond bond2-MeO-phenyl 1520  —CH₂CH₂CH₂— bond bond 3-MeO-phenyl 1521  —CH₂CH₂CH₂—bond bond 4-MeO-phenyl 1522  —CH₂CH₂CH₂— bond bond 2-MeS-phenyl 1523 —CH₂CH₂CH₂— bond bond 3-MeS-phenyl 1524  —CH₂CH₂CH₂— bond bond4-MeS-phenyl 1525  —CH₂CH₂CH₂— bond bond 2-F₃C-phenyl 1526  —CH₂CH₂CH₂—bond bond 3-F₃C-phenyl 1527  —CH₂CH₂CH₂— bond bond 4-F₃C-phenyl 1528 —CH₂CH₂CH₂— bond bond 2,3-diF-phenyl 1529  —CH₂CH₂CH₂— bond bond2,4-diF-phenyl 1530  —CH₂CH₂CH₂— bond bond 2 5-diF-phenyl 1531 —CH₂CH₂CH₂— bond bond 2,6-diF-phenyl 1532  —CH₂CH₂CH₂— bond bond3,4-diF-phenyl 1533  —CH₂CH₂CH₂— bond bond 3,5-diF-phenyl 1534 —CH₂CH₂CH₂— bond bond 2,3-diCl-phenyl 1535  —CH₂CH₂CH₂— bond bond2,4-diCl-phenyl 1536  —CH₂CH₂CH₂— bond bond 2,5-diCl-phenyl 1537 —CH₂CH₂CH₂— bond bond 2,6-diCl-phenyl 1538  —CH₂CH₂CH₂— bond bond3,4-diCl-phenyl 1539  —CH₂CH₂CH₂— bond bond 3,5-diCl-phenyl 1540 —CH₂CH₂CH₂— bond bond 2-Cl-3-F-phenyl 1541  —CH₂CH₂CH₂— bond bond2-Cl-4-F-phenyl 1542  —CH₂CH₂CH₂— bond bond 2-Cl-5-F-phenyl 1543 —CH₂CH₂CH₂— bond bond 3-Cl-4-F-phenyl 1544  —CH₂CH₂CH₂— bond bond3-Cl-5-F-phenyl 1545  —CH₂CH₂CH₂— bond bond 4-Cl-2-F-phenyl 1546 —CH₂CH₂CH₂— bond bond 4-Cl-3-F-phenyl 1547  —CH₂CH₂CH₂— bond bond2,3-diMeO-phenyl 1548  —CH₂CH₂CH₂— bond bond 2,4-diMeO-phenyl 1549 —CH₂CH₂CH₂— bond bond 2,5-diMeO-phenyl 1550  —CH₂CH₂CH₂— bond bond2,6-diMeO-phenyl 1551  —CH₂CH₂CH₂— bond bond 3,4-diMeO-phenyl 1552 —CH₂CH₂CH₂— bond bond 3,5-diMeO-phenyl 1553  —CH₂CH₂CH₂— bond bondcyclopropyl 1554  —CH₂CH₂CH₂— bond bond cyclobutyl 1555  —CH₂CH₂CH₂—bond bond cyclopentyl 1556  —CH₂CH₂CH₂— bond bond cyclohexyl 1557 —CH₂CH₂CH₂— bond bond 2-furanyl 1558  —CH₂CH₂CH₂— bond bond 2-thienyl1559  —CH₂CH₂CH₂— bond bond 2-imidazolyl 1560  —CH₂CH₂CH₂— bond bond2-pyridyl 1561  —CH₂CH₂CH₂— bond bond 3-pyridyl 1562  —CH₂CH₂CH₂— bondbond 4-pyridyl 1563  —CH₂CH₂CH₂— bond bond N-morpholinyl 1564 —CH₂CH₂CH₂— bond bond N-piperidinyl 1565  —CH₂CH₂CH₂— bond bond3-Me-2-pyridyl 1566  —CH₂CH₂CH₂— bond bond 4-Me-2-pyridyl 1567 —CH₂CH₂CH₂— bond bond 1-indolyl 1568  —CH₂CH₂CH₂— bond bond2-benzothienyl 1569  —CH₂CH₂CH₂— bond bond 2-benzofuranyl 1570 —CH₂CH₂CH₂— bond bond 1-benzimidazole 1571  —CH₂CH₂CH₂— bond bond2-naphthyl 1572  —CH₂CH₂— bond —O— phenyl 1573  —CH₂CH₂— bond —O—3,3-diphenylmethyl 1574  —CH₂CH₂— bond 2-F-phenyl 1575  —CH₂CH₂— bond—O— 3-F-phenyl 1576  —CH₂CH₂— bond —O— 4-F-phenyl 1577  —CH₂CH₂— bond—O— 2-Cl-phenyl 1578  —CH₂CH₂— bond —O— 3-Cl-phenyl 1579  —CH₂CH₂— bond—O— 4-Cl-phenyl 1580  —CH₂CH₂— bond —O— 2-Me-phenyl 1581  —CH₂CH₂— bond—O— 3-Me-phenyl 1582  —CH₂CH₂— bond —O— 4-Me-phenyl 1583  —CH₂CH₂— bond—O— 2-MeO-phenyl 1584  —CH₂CH₂— bond —O— 3-MeO-phenyl 1585  —CH₂CH₂—bond —O— 4-MeO-phenyl 1586  —CH₂CH₂— bond —O— 2-MeS-phenyl 1587 —CH₂CH₂— bond —O— 3-MeS-phenyl 1588  —CH₂CH₂— bond —O— 4-MeS-phenyl1589  —CH₂CH₂— bond —O— 2-F₃C-phenyl 1590  —CH₂CH₂— bond —O—3-F₃C-phenyl 1591  —CH₂CH₂— bond —O— 4-F₃C-phenyl 1592  —CH₂CH₂— bond—O— 2,3-diF-phenyl 1593  —CH₂CH₂— bond —O— 2,4-diF-phenyl 1594  —CH₂CH₂—bond —O— 2,5-diF-phenyl 1595  —CH₂CH₂— bond —O— 2,6-diF-phenyl 1596 —CH₂CH₂— bond —O— 3,4-diF-phenyl 1597  —CH₂CH₂— bond —O— 3,5-diF-phenyl1598  —CH₂CH₂— bond —O— 2,3-diCl-phenyl 1599  —CH₂CH₂— bond —O—2,4-diCl-phenyl 1600  —CH₂CH₂— bond —O— 2,5-diCl-phenyl 1601  —CH₂CH₂—bond —O— 2,6-diCl-phenyl 1602  —CH₂CH₂— bond —O— 3,4-diCl-phenyl 1603 —CH₂CH₂— bond —O— 3,5-diCl-phenyl 1604  —CH₂CH₂— bond —O—2-Cl-3-F-phenyl 1605  —CH₂CH₂— bond —O— 2-Cl-4-F-phenyl 1606  —CH₂CH₂—bond —O— 2-Cl-5-F-phenyl 1607  —CH₂CH₂— bond —O— 3-Cl-4-F-phenyl 1608 —CH₂CH₂— bond —O— 3-Cl-5-F-phenyl 1609  —CH₂CH₂— bond —O—4-Cl-2-F-phenyl 1610  —CH₂CH₂— bond —O— 4-Cl-3-F-phenyl 1611  —CH₂CH₂—bond —O— 2,3-diMeO-phenyl 1612  —CH₂CH₂— bond —O— 2,4-diMeO-phenyl 1613 —CH₂CH₂— bond —O— 2,5-diMeO-phenyl 1614  —CH₂CH₂— bond —O—2,6-diMeO-phenyl 1615  —CH₂CH₂— bond —O— 3,4-diMeO-phenyl 1616  —CH₂CH₂—bond —O— 3,5-diMeO-phenyl 1617  —CH₂CH₂— bond —O— cyclopropyl 1618 —CH₂CH₂— bond —O— cyclobutyl 1619  —CH₂CH₂— bond —O— cyclopentyl 1620 —CH₂CH₂— bond —O— cyclohexyl 1621  —CH₂CH₂— bond —O— 2-furanyl 1622 —CH₂CH₂— bond —O— 2-thienyl 1623  —CH₂CH₂— bond —O— 2-pyridyl 1624 —CH₂CH₂— bond —O— 3-pyridyl 1625  —CH₂CH₂— bond —O— 4-pyridyl 1626 —CH₂CH₂— bond —O— 3-Me-2-pyridyl 1627  —CH₂CH₂— bond —O— 4-Me-2-pyridyl1628  —CH₂CH₂— bond —O— 2-benzothienyl 1629  —CH₂CH₂— bond —O—2-benzofuranyl 1630  —CH₂CH₂— bond —O— 2-naphthyl 1631  —CH₂CH₂CH₂— bond—O— phenyl 1632  —CH₂CH₂CH₂— bond —O— 3,3-diphenylmethyl 1633 —CH₂CH₂CH₂— bond —O— 2-F-phenyl 1634  —CH₂CH₂CH₂— bond —O— 3-F-phenyl1635  —CH₂CH₂CH₂— bond —O— 4-F-phenyl 1636  —CH₂CH₂CH₂— bond —O—2-Cl-phenyl 1637  —CH₂CH₂CH₂— bond —O— 3-Cl-phenyl 1638  —CH₂CH₂CH₂—bond —O— 4-Cl-phenyl 1639  —CH₂CH₂CH₂— bond —O— 2-Me-phenyl 1640 —CH₂CH₂CH₂— bond —O— 3-Me-phenyl 1641  —CH₂CH₂CH₂— bond —O— 4-Me-phenyl1642  —CH₂CH₂CH₂— bond —O— 2-MeO-phenyl 1643  —CH₂CH₂CH₂— bond —O—3-MeO-phenyl 1644  —CH₂CH₂CH₂— bond —O— 4-MeO-phenyl 1645  —CH₂CH₂CH₂—bond —O— 2-MeS-phenyl 1646  —CH₂CH₂CH₂— bond —O— 3-MeS-phenyl 1647 —CH₂CH₂CH₂— bond —O— 4-MeS-phenyl 1648  —CH₂CH₂CH₂— bond —O—2-F₃C-phenyl 1649  —CH₂CH₂CH₂— bond —O— 3-F₃C-phenyl 1650  —CH₂CH₂CH₂—bond —O— 4-F₃C-phenyl 1651  —CH₂CH₂CH₂— bond —O— 2,3-diF-phenyl 1652 —CH₂CH₂CH₂— bond —O— 2,4-diF-phenyl 1653  —CH₂CH₂CH₂— bond —O—2,5-diF-phenyl 1654  —CH₂CH₂CH₂— bond —O— 2,6-diF-phenyl 1655 —CH₂CH₂CH₂— bond —O— 3,4-diF-phenyl 1656  —CH₂CH₂CH₂— bond —O—3,5-diF-phenyl 1657  —CH₂CH₂CH₂— bond —O— 2,3-diCl-phenyl 1658 —CH₂CH₂CH₂— bond —O— 2,4-diCl-phenyl 1659  —CH₂CH₂CH₂— bond —O—2,5-diCl-phenyl 1660  —CH₂CH₂CH₂— bond —O— 2,6-diCl-phenyl 1661 —CH₂CH₂CH₂— bond —O— 3,4-diCl-phenyl 1662  —CH₂CH₂CH₂— bond —O—3,5-diCl-phenyl 1663  —CH₂CH₂CH₂— bond —O— 2-Cl-3-F-phenyl 1664 —CH₂CH₂CH₂— bond —O— 2-Cl-4-F-phenyl 1665  —CH₂CH₂CH₂— bond —O—2-Cl-5-F-phenyl 1666  —CH₂CH₂CH₂— bond —O— 3-Cl-4-F-phenyl 1667 —CH₂CH₂CH₂— bond —O— 3-Cl-5-F-phenyl 1668  —CH₂CH₂CH₂— bond —O—4-Cl-2-F-phenyl 1669  —CH₂CH₂CH₂— bond —O— 4-Cl-3-F-phenyl 1670 —CH₂CH₂CH₂— bond —O— 2,3-diMeO-phenyl 1671  —CH₂CH₂CH₂— bond —O—2,4-diMeO-phenyl 1672  —CH₂CH₂CH₂— bond —O— 2,5-diMeO-phenyl 1673 —CH₂CH₂CH₂— bond —O— 2,6-diMeO-phenyl 1674  —CH₂CH₂CH₂— bond —O—3,4-diMeO-phenyl 1675  —CH₂CH₂CH₂— bond —O— 3,5-diMeO-phenyl 1676 —CH₂CH₂CH₂— bond —O— cyclopropyl 1677  —CH₂CH₂CH₂— bond —O— cyclobutyl1678  —CH₂CH₂CH₂— bond —O— cyclopentyl 1679  —CH₂CH₂CH₂— bond —O—cyclohexyl 1680  —CH₂CH₂CH₂— bond —O— 2-furanyl 1681  —CH₂CH₂CH₂— bond—O— 2-thienyl 1682  —CH₂CH₂CH₂— bond —O— 2-pyridyl 1683  —CH₂CH₂CH₂—bond —O— 3-pyridyl 1684  —CH₂CH₂CH₂— bond —O— 4-pyridyl 1685 —CH₂CH₂CH₂— bond —O— 3-Me-2-pyridyl 1686  —CH₂CH₂CH₂— bond —O—4-Me-2-pyridyl 1687  —CH₂CH₂CH₂— bond —O— 2-benzothienyl 1688 —CH₂CH₂CH₂— bond —O— 2-benzofuranyl 1689  —CH₂CH₂CH₂— bond —O—2-naphthyl

1. (canceled)
 2. A compound of Formula (I)

or a pharmaceutically acceptable salt form thereof, wherein A is O; Q is—NR¹R²; R¹, at each occurrence, is independently selected from: H; C₁-C₆alkyl substituted with 0-3 R^(1a); C₂-C₆ alkenyl substituted with 0-3R^(1a); R^(1a), at each occurrence, is independently selected from H,OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃; C₃-C₆ cycloalkyl substituted with 0-3 R^(1b);phenyl substituted with 0-3 R^(1b); and 5 to 6 membered heterocyclesubstituted with 0-3 R^(1b); R^(1b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R² isindependently selected from H, NH₂, OH, C₁-C₆ alkyl, C₁-C₆ alkoxy,phenoxy, and benzyloxy; R³ is (CR⁷R^(7a))_(n)—R⁴,—(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—S(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—S(═O)₂—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—C(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—NHC(═O)—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—C(═O)NH—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—NHS(═O)₂—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(n)—S(═O)₂NH—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, 2, or 3; n is0, 1, 2, or 3; R^(3a) is H, OH, OH, C₁-C₄ alkyl, C₁-C₄ alkoxy, or C₂-C₄alkenyloxy; R⁴ is H, OH, OR^(14a), C₁-C₆ alkyl substituted with 0-3R^(4a), C₂-C₆ alkenyl substituted with 0-3 R^(4a), C₂-C₆ alkynylsubstituted with 0-3 R^(4a), C₁-C₁₀ carbocycle substituted with 0-3R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, F, Cl, Br, I, CF₃, C₁-C₁₀ carbocyclesubstituted with 0-3 R^(4b), aryl substituted with 0-3 R^(4b), or 5 to10 membered heterocycle substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R⁵ is H, OR¹⁴; C₁-C₆alkyl substituted with 0-3 R^(5b); C₁-C₆ alkoxy substituted with 0-3R^(5b); C₂-C₆ alkenyl substituted with 0-3 R^(5b); C₂-C₆ alkynylsubstituted with 0-3 R^(5b); C₃-C₁₀ carbocycle substituted with 0-3R^(5c); aryl substituted with 0-3 R^(5c); or 5 to 10 memberedheterocycle substituted with 0-3R^(5c); R^(5a) is H, OH, C₁-C₄ alkyl,C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄ alkenyloxy; R^(5b), at eachoccurrence, is independently selected from: H, C₁-C₆ alkyl, CF₃, OR¹⁴,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶; C₃-C₁₀ carbocycle substituted with0-3 R^(5c); aryl substituted with 0-3 R^(5c); or 5 to 10 memberedheterocycle substituted with 0-3 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, and C₁-C₄ haloalkoxy; R⁶ is H; C₁-C₆ alkyl substituted with0-3 R^(6a); C₃-C₆ carbocycle substituted with 0-3 R^(6b); or arylsubstituted with 0-3R^(6b); R^(6a), at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶,phenyl or CF₃; R^(6b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R⁷, at each occurrence,is independently selected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, andC₁-C₄ alkyl; R^(7a), at each occurrence, is independently selected fromH, OH, Cl, F, Br, I, CN, NO₂, CF₃, aryl and C₁-C₄ alkyl; R^(7b) isindependently selected from H and C₁-C₄ alkyl; W is —(CR⁸R^(8a))_(p)—; pis 0, 1, 2, 3, or 4; R⁸ and R^(8a), at each occurrence, areindependently selected from H, F, C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄alkynyl and C₃-C₈ cycloalkyl; X is a bond; aryl substituted with 0-3R^(Xb); C₃-C₁₀ carbocycle substituted with 0-3 R^(Xb); or 5 to 10membered heterocycle substituted with 0-2 R^(Xb); R^(Xb), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; Y is a bond or—(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, 2, or 3; u is 0, 1, 2,or 3; R⁹ and R^(9a), at each occurrence, are independently selected fromH, F, C₁-C₆ alkyl or C₃-C₈ cycloalkyl; V is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b), —NR^(19b)C(═O)—,—NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b), —NR^(19b)S(═O)—, —S(═O)NR^(19b)—,—C(═O)O—, or —OC(═O)—; Z is C₁-C₃ alkyl substituted with 1-2 R¹²; arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R¹² is aryl substituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substitutedwith 0-4 R^(12b); or 5 to 10 membered heterocycle substituted with 0-3R^(12b); R^(12b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄haloalkoxy; B is

R¹¹, at each occurrence, is independently selected from C₁-C₄ alkoxy,Cl, F, Br, I, ═O, CN, NO₂, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹,S(═O)₂NR¹⁸R¹⁹, CF₃; C₁-C₆ alkyl substituted with 0-1 R^(11a); arylsubstituted with 0-3 R^(11b); C₃-C₁₀ carbocycle substituted with 0-3R^(11b); or 5 to 10 membered heterocycle substituted with 0-3 R^(11b);alternatively, two R¹¹ substituents on the same or adjacent carbon atomsmay be combined to form a C₃-C₆ carbocycle or a benzo fused radical;R^(11a), at each occurrence, is independently selected from H, C₁-C₆alkyl, OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenylsubstituted with 0-3 R^(11b); R^(11b), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R¹⁴ isH, phenyl, benzyl, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl; R¹⁵, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆ alkyl); R¹⁶, at eachoccurrence, is independently selected from H, OH, C₁-C₆ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆ alkyl); R¹⁷ is H,aryl, (aryl)CH₂—, C₁-C₆ alkyl, or C₂-C₆ alkoxyalkyl; R¹⁸, at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆ alkyl); and R¹⁹, ateach occurrence, is independently selected from H, OH, C₁-C₆ alkyl,phenyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆alkyl); and R^(19b) is H, C₁-C₆ alkyl, C₃-C₈ cycloalkyl, phenyl, benzylor phenethyl.
 3. A compound of claim 2 of Formula (Ia)

or a pharmaceutically acceptable salt thereof, wherein: R³ is(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, or 2; m is 0,1, or 2; R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, or butoxy; R⁴ is H, OH, OR^(14a), C₁-C₄ alkyl substituted with0-2 R^(4a), C₂-C₄ alkenyl substituted with 0-2 R^(4a), C₂-C₄ alkynylsubstituted with 0-2 R^(4a), C₃-C₆ cycloalkyl substituted with 0-3R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, F, Cl, Br, I CF₃, C₃-C₁₀ carbocyclesubstituted with 0-3 R^(4b), aryl substituted with 0-3 R^(4b), or 5 to10 membered heterocycle substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R⁵ is H, OR¹⁴; C₁-C₆alkyl substituted with 0-3 R^(5b); C₂-C₆ alkenyl substituted with 0-3R^(5b); C₂-C₆ alkynyl substituted with 0-3 R^(5b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(5c); aryl substituted with 0-3 R^(5c); or 5 to10 membered heterocycle substituted with 0-3R^(5c); R^(5a) is H, OH,C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄ alkenyloxy; R^(5b),at each occurrence, is independently selected from: H, C₁-C₆ alkyl, CF₃,OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶; C₃-C₁₀ carbocycle substitutedwith 0-3 R^(5c); aryl substituted with 0-3 R^(5c); or 5 to 10 memberedheterocycle substituted with 0-3 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, and C₁-C₄ haloalkoxy; R⁶ is H, methyl, or ethyl; R⁷, at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,CF₃, and C₁-C₄ alkyl; R^(7a), at each occurrence, is independentlyselected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;R^(7b) is independently selected from H, methyl, ethyl, propyl, andbutyl; W is —(CR⁸R^(8a))_(p)—; p is 0, 1, or 2; R⁸ and R^(8a), at eachoccurrence, are independently selected from H, F, C₁-C₃ alkyl, C₂-C₃alkenyl, C₂-C₃ alkynyl and C₃-C₆ cycloalkyl; X is a bond; arylsubstituted with 0-3 R^(Xb); C₃-C₁₀ carbocycle substituted with 0-2R^(Xb); or 5 to 10 membered heterocycle substituted with 0-2 R^(Xb);R^(Xb), at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; Y is a bondor —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, or 2; u is 0, 1, or2; R⁹ and R^(9a), at each occurrence, are independently selected from H,F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl; V is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —N(R¹⁹)—, —C(═O)NR^(19b)—, NR^(19b)C(═O)—,—NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;Z is C₁-C₃ alkyl substituted with 1-2 R¹²; aryl substituted with 0-4R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10membered heterocycle substituted with 0-3 R^(12b); R¹² is arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; B is

R¹¹, at each occurrence, is independently selected from C₁-C₄ alkoxy,Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,CF₃; C₁-C₆ alkyl substituted with 0-1 R^(11a); aryl substituted with 0-3R^(11b); C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or 5 to 10membered heterocycle substituted with 0-3 R^(11b); alternatively, twoR¹¹ substituents on the same or adjacent carbon atoms may be combined toform a C₃-C₆ carbocycle or a benzo fused radical; R^(11a), at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F,Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3R^(11b); R^(11b), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R¹⁴ is H, phenyl, benzyl, C₁-C₆alkyl, or C₂-C₆ alkoxyalkyl; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl)and —S(═O)₂—(C₁-C₆ alkyl); R¹⁶, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆alkyl) and —S(═O)₂—(C₁-C₆ alkyl); R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆alkyl, or C₂-C₆ alkoxyalkyl; R¹⁸, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl)and —S(═O)₂—(C₁-C₆ alkyl); and R¹⁹, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, phenyl, benzyl, phenethyl,—C(═O)—(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆ alkyl); and R^(19b) is H, C₁-C₆alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or phenethyl.
 4. A compound ofclaim 3 or a pharmaceutically acceptable salt form thereof, wherein: R³is —(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(n)—N(R^(7b))-(CR⁷R^(7a))_(m)—R⁴; n is 0 or 1; m is 0 or 1;R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy,or butoxy; R⁴ is H, OH, C₁-C₄ alkyl substituted with 0-2 R^(4a), C₂-C₄alkenyl substituted with 0-2 R^(4a), C₂-C₄ alkynyl substituted with 0-1R^(4a), C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), aryl substitutedwith 0-3 R^(4b), or 5 to 10 membered heterocycle substituted with 0-3R^(4b); R^(4a), at each occurrence, is independently selected from is H,F, Cl, CF₃, C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), phenylsubstituted with 0-3 R^(4b), or 5 to 6 membered heterocycle substitutedwith 0-3 R^(4b); R^(4b), at each occurrence, is independently selectedfrom H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R⁵ is H, OR¹⁴; C₁-C₄ alkyl substituted with 0-3 R^(5b);C₂-C₄ alkenyl substituted with 0-2 R^(5b); or C₂-C₄ alkynyl substitutedwith 0-2 R^(5b); R^(5a) is H, OH, methyl, ethyl, propyl, butyl, methoxy,ethoxy, propoxy, butoxy, or allyl; R^(5b), at each occurrence, isindependently selected from: H, methyl, ethyl, propyl, butyl, CF₃, OR¹⁴,═O; C₃-C₆ cycloalkyl substituted with 0-2 R^(5c); phenyl substitutedwith 0-3 R^(5c); or 5 to 6 membered heterocycle substituted with 0-2R^(5c); R^(5c), at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃,S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R⁶ is H; R⁷, at each occurrence, is independently selectedfrom H, F, CF₃, methyl, and ethyl; R^(7a), at each occurrence, isindependently selected from H, F, CF₃, methyl, and ethyl; R^(7b) isindependently selected from H, methyl, and ethyl; W is a bond, —CH₂—,—CH(CH₃)—, —CH₂CH₂— or —CH(CH₃)CH₂—; X is a bond; phenyl substitutedwith 0-2 R^(Xb); C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6membered heterocycle substituted with 0-2 R^(Xb); R^(Xb), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂haloalkyl, and C₁-C₂ haloalkoxy; Y is a bond, —CH₂—V—, —V—, or —V—CH₂—;V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or—N(CH₂CH₃)—, Z is C₁-C₂ alkyl substituted with 1-2 R¹²; aryl substitutedwith 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to10 membered heterocycle substituted with 0-3 R^(12b); R¹² is arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; B is

R¹¹, at each occurrence, is independently selected from C₁-C₄ alkoxy,Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃; C₁-C₄ alkyl substitutedwith 0-1 R^(11a); phenyl substituted with 0-3 R^(1b); C₃-C₆ carbocyclesubstituted with 0-3 R^(11b); or 5 to 6 membered heterocycle substitutedwith 0-3 R^(11b); alternatively, two R¹¹ substituents on the same oradjacent carbon atoms may be combined to form a cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, or a benzo fused radical; R^(11a), at eachoccurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴, F, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹⁴ isH, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R¹⁵, at eachoccurrence, is independently selected from H, C₁-C₄ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄ alkyl); R¹⁶, at eachoccurrence, is independently selected from H, OH, C₁-C₄ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄ alkyl); R¹⁷ is H,phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,(4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, orethoxyethyl; R¹⁸, at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and R¹⁹, ateach occurrence, is independently selected from H, methyl, and ethyl. 5.A compound of claim 4 of Formula (Ib)

or a pharmaceutically acceptable salt thereof, wherein: R³ is —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃,—CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CF₃, —CH₂CF₃, —CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃,—CH═CH₂, —CH₂CH═CH₂, —CH₂C(CH₃)═CH₂, —CH₂CH═C(CH₃)₂, —CH₂CH₂CH═CH₂,—CH₂CH₂C(CH₃)═CH₂, —CH₂CH₂CH═C(CH₃)₂, cis-CH₂CH═CH(CH₃),cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃), trans-CH₂CH₂CH═CH(CH₃);—C≡CH, —CH₂C≡CH, —CH₂C═C(CH₃), cyclopropyl-CH₂—, cyclobutyl-CH₂—,cyclopentyl-CH₂—, cyclohexyl-CH₂—, cyclopropyl-CH₂CH₂—,cyclobutyl-CH₂CH₂-cyclopentyl-CH₂CH₂—, cyclohexyl-CH₂CH₂—, phenyl-CH₂—,(2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—,(2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,(3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—,(2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,(3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,(3-F-5-Cl-phenyl)CH₂—, (3-Cl-4-F-phenyl)CH₂—, phenyl-CH₂CH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—, or R⁵ is —CH₃,—CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₃)₂, —CH₂CH₂CH₂CH₃, —CH(CH₃)CH₂CH₃,—CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CH₂CH₂CH₂CH₂CH₃, —CH(CH₃)CH₂CH₂CH₃,—CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂, —CH(CH₂CH₃)₂, —CH₂CF₃, —CH₂CH₂CF₃,—CH₂CH₂CH₂CF₃, —CH₂CH₂CH₂CH₂CF₃, —CH═CH₂, —CH₂CH═CH₂, —CH═CHCH₃,cis-CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃), trans-CH₂CH═CH(C₆H₅),—CH₂CH═C(CH₃)₂, cis-CH₂CH═CHCH₂CH₃, trans-CH₂CH═CHCH₂CH₃,cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH₂CH═CH(CH₃), trans-CH₂CH═CHCH₂ (C₆H₅),—C≡CH, —CH₂C≡CH, —CH₂C═C(CH₃), —CH₂C═C(C₆H₅) —CH₂CH₂C≡CH,—CH₂CH₂C═C(CH₃), —CH₂CH₂C═C(C₆H₅) —CH₂CH₂CH₂C≡CH, —CH₂CH₂CH₂C═C(CH₃),—CH₂CH₂CH₂C═C(C₆H₅) cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, (2-CH₃-cyclopropyl)CH₂—, (3-CH₃-cyclobutyl) CH₂—,cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—, cyclopentyl-CH₂CH₂—,cyclohexyl-CH₂CH₂—, (2-CH₃-cyclopropyl)CH₂CH₂—,(3-CH₃-cyclobutyl)CH₂CH₂—, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, furanyl-CH₂—, thienyl-CH₂—,pyridyl-CH₂—, 1-imidazolyl-CH₂—, oxazolyl-CH₂—, isoxazolyl-CH₂—,phenyl-CH₂CH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,(4-F-phenyl)CH₂CH₂—, furanyl-CH₂CH₂—, thienyl-CH₂CH₂—, pyridyl-CH₂CH₂—,1-imidazolyl-CH₂CH₂—, oxazolyl-CH₂CH₂—, isoxazolyl-CH₂CH₂—, W is a bond,—CH₂—, or —CH(CH₃)—; X is a bond;

Y is a bond, —CH₂—V—, —V—, or —V—CH₂—; V is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —NH—, or —N(CH₃)—, Z is phenyl 2-F-phenyl,3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl, 3-Cl-phenyl, 4-Cl-phenyl,2,3-diF-phenyl, 2,4-diF-phenyl, 2,5-diF-phenyl, 2,6-diF-phenyl,3,4-diF-phenyl, 3,5-diF-phenyl, 2,3-diCl-phenyl, 2,4-diCl-phenyl,2,5-diCl-phenyl, 2,6-diCl-phenyl, 3,4-diCl-phenyl, 3,5-diCl-phenyl,3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl, 3-Cl-4-F-phenyl, 2-MeO-phenyl,3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl, 3-Me-phenyl, 4-Me-phenyl,2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl, 2-CF₃O-phenyl, 3-CF₃O-phenyl,4-CF₃O-phenyl, furanyl, thienyl, pyridyl, 2-Me-pyridyl, 3-Me-pyridyl,4-Me-pyridyl, 1-imidazolyl, oxazolyl, isoxazolyl, 1-benzimidazolyl,cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, morpholino,N-piperinyl, phenyl-CH₂—, (2-F-phenyl)CH₂—, (3-F-phenyl)CH₂—,(4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—, (3-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—, (2,4-diF-phenyl)CH₂—,(2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—, (3,4-diF-phenyl)CH₂—,(3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—, (2,4-diCl-phenyl)CH₂—,(2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—, (3,4-diCl-phenyl)CH₂—,(3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—, (3-F-5-Cl-phenyl)CH₂—,(3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—, (3-MeO-phenyl)CH₂—,(4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—, (3-Me-phenyl)CH₂—,(4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—, (3-MeS-phenyl)CH₂—,4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—, (3-CF₃O-phenyl)CH₂—,(4-CF₃O-phenyl)CH₂—, (furanyl)CH₂—, (thienyl)CH₂—, (pyridyl)CH₂—,(2-Me-pyridyl)CH₂—, (3-Me-pyridyl)CH₂—, (4-Me-pyridyl)CH₂—,(1-imidazolyl)CH₂—, (oxazolyl)CH₂—, (isoxazolyl)CH₂—,(1-benzimidazolyl)CH₂—, (cyclopropyl)CH₂—, (cyclobutyl)CH₂—,(cyclopentyl)CH₂—, (cyclohexyl)CH₂—, (morpholino)CH₂—,(N-pipridinyl)CH₂—, phenyl-CH₂CH₂—, (phenyl)₂CHCH₂—,(2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—, (4-F-phenyl)CH₂CH₂—,(2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—, (4-Cl-phenyl)CH₂CH₂—,(2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (furanyl)CH₂CH₂—, (thienyl)CH₂CH₂—,(pyridyl)CH₂CH₂—, (2-Me-pyridyl)CH₂CH₂—, (3-Me-pyridyl)CH₂CH₂—,(4-Me-pyridyl)CH₂CH₂—, (imidazolyl)CH₂CH₂—, (oxazolyl)CH₂CH₂—,(isoxazolyl)CH₂CH₂—, (benzimidazolyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—,(cyclobutyl)CH₂CH₂—, (cyclopentyl)CH₂CH₂—, (cyclohexyl)CH₂CH₂—,(morpholino)CH₂CH₂—, (N-pipridinyl)CH₂CH₂—, B is

R¹¹, at each occurrence, is independently selected from H, ═O, methyl,ethyl, phenyl, benzyl, phenethyl, 4-F-phenyl, (4-F-phenyl)CH₂—,(4-F-phenyl)CH₂CH₂—, 4-Cl-phenyl, (4-Cl-phenyl)CH₂—,(4-Cl-phenyl)CH₂CH₂—, 4-CH₃-phenyl, (4-CH₃-phenyl)CH₂—,(4-CH₃-phenyl)CH₂CH₂—, 4-CF₃-phenyl, (4-CF₃-phenyl)CH₂—, or(4-CF₃-phenyl)CH₂CH₂—; and alternatively, two R¹¹ substituents on thesame or adjacent carbon atoms may be combined to form a cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, or a benzo fused radical. 6.-8.(canceled)
 9. A compound of claim 4 of Formula (Ie) wherein:

or a pharmaceutically acceptable salt or prodrug thereof, wherein: R³ isR⁴, R⁴ is C₁-C₄ alkyl substituted with 0-2 R^(4a), C₂-C₄ alkenylsubstituted with 0-2 R^(4a), C₂-C₄ alkynyl substituted with 0-2 R^(4a),R^(4a), at each occurrence, is independently selected from is H, F, CF₃,C₃-C₆ cycloalkyl substituted with 0-3 R^(4b), phenyl substituted with0-3 R^(4b), or 5 to 6 membered heterocycle substituted with 0-3 R^(4b);R^(4b), at each occurrence, is independently selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl,butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b); C₂-C₄ alkenyl substitutedwith 0-2 R^(5b); or C₂-C₄ alkynyl substituted with 0-2 R^(5b); R^(5b),at each occurrence, is independently selected from: H, methyl, ethyl,propyl, butyl, CF₃, OR¹⁴, ═O; C₃-C₆ cycloalkyl substituted with 0-2R^(5c); phenyl substituted with 0-3 R^(5c); or 5 to 6 memberedheterocycle substituted with 0-2 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is —CH₂— or —CH(CH₃)—;X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆ cycloalkylsubstituted with 0-2 R^(Xb); or 5 to 6 membered heterocycle substitutedwith 0-2 R^(Xb); R^(Xb), at each occurrence, is independently selectedfrom H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl,and C₁-C₂ haloalkoxy; Y is a bond, —CH₂—V—, —V—, or —V—CH₂—; V is abond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or—N(CH₂CH₃)—, Z is C₁-C₂ alkyl substituted with 1-2 R¹²; aryl substitutedwith 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to10 membered heterocycle substituted with 0-3 R^(12b); R¹² is arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R¹¹ is methoxy, ethoxy, propoxy, butoxy, Cl, F, ═O, NR¹⁸R¹⁹,CF₃; C₁-C₄ alkyl substituted with 0-1 R^(11a); phenyl substituted with0-3 R^(11b); C₃-C₆ carbocycle substituted with 0-3 R^(11b); or 5 to 6membered heterocycle substituted with 0-3 R^(11b); R^(11a), at eachoccurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴, F, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,methyl, ethyl, propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl,and C₁-C₂ haloalkoxy; R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl,butyl; R¹⁵, at each occurrence, is independently selected from H,methyl, ethyl, propyl, and butyl; R¹⁶, at each occurrence, isindependently selected from H, OH, C₁-C₄ alkyl, benzyl, phenethyl,—C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄ alkyl); R¹⁸, at each occurrence,is independently selected from H, methyl, ethyl, propyl, butyl, phenyl,benzyl, and phenethyl; and R¹⁹, at each occurrence, is independentlyselected from H, methyl, and ethyl.
 10. (canceled)
 11. A compound ofclaim 2 of Formula (IIa)

or a pharmaceutically acceptable salt thereof, wherein: R³ is—(CR⁷R^(7a))_(n)—R⁴, —(CR⁷R^(7a))_(n)—S—(CR⁷R^(7a))_(m)—R⁴,—(CR⁷R^(7a))_(n)—O—(CR⁷R^(7a))_(m)—R⁴, or—(CR⁷R^(7a))_(n)—N(R^(7b))—(CR⁷R^(7a))_(m)—R⁴; n is 0, 1, or 2; m is 0,1, or 2; R^(3a) is H, OH, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, or butoxy; R⁴ is H, OH, OR^(14a), C₁-C₄ alkyl substituted with0-2 R^(4a), C₂-C₄ alkenyl substituted with 0-2 R^(4a), C₂-C₄ alkynylsubstituted with 0-2 R^(4a), C₃-C₆ cycloalkyl substituted with 0-3R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, F, Cl, Br, I CF₃, C₃-C₁₀ carbocyclesubstituted with 0-3 R^(4b), aryl substituted with 0-3 R^(4b), or 5 to10 membered heterocycle substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R⁵ is H, OR¹⁴; C₁-C₆alkyl substituted with 0-3 R^(5b); C₂-C₆ alkenyl substituted with 0-3R^(5b); C₂-C₆ alkynyl substituted with 0-3 R^(5b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(5c); aryl substituted with 0-3 R^(5c); or 5 to10 membered heterocycle substituted with 0-3R^(5c); R^(5a) is H, OH,C₁-C₄ alkyl, C₁-C₄ alkoxy, C₂-C₄ alkenyl, or C₂-C₄ alkenyloxy; R^(5b),at each occurrence, is independently selected from: H, C₁-C₆ alkyl, CF₃,OR¹⁴, Cl, F, Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶; C₃-C₁₀ carbocycle substitutedwith 0-3 R^(5c); aryl substituted with 0-3 R^(5c); or 5 to 10 memberedheterocycle substituted with 0-3 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄haloalkyl, and C₁-C₄ haloalkoxy; R⁶ is H, methyl, or ethyl; R⁷, at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,CF₃, and C₁-C₄ alkyl; R^(7a), at each occurrence, is independentlyselected from H, OH, Cl, F, Br, I, CN, NO₂, CF₃, phenyl and C₁-C₄ alkyl;R^(7b) is independently selected from H, methyl, ethyl, propyl, andbutyl; W is —(CR⁸R^(8a))_(p)—; p is 0, 1, or 2; R⁸ and R^(8a), at eachoccurrence, are independently selected from H, F, C₁-C₃ alkyl, C₂-C₃alkenyl, C₂-C₃ alkynyl and C₃-C₆ cycloalkyl; X is a bond; arylsubstituted with 0-3 R^(Xb); C₃-C₁₀ carbocycle substituted with 0-2R^(Xb); or 5 to 10 membered heterocycle substituted with 0-2 R^(Xb);R^(Xb), at each occurrence, is independently selected from H, OH, Cl, F,Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₆alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; Y is a bondor —(CR⁹R^(9a))_(t)—V—(CR⁹R^(9a))_(u)—; t is 0, 1, or 2; u is 0, 1, or2; R⁹ and R^(9a), at each occurrence, are independently selected from H,F, C₁-C₄ alkyl or C₃-C₆ cycloalkyl; V is a bond, —C(═O)—, —O—, —S—,—S(═O)—, —S(═O)₂—, —N(R¹⁹)—, C(═O)NR^(19b)—, NR^(19b)C(═O)—,—NR^(19b)S(═O)₂—, —S(═O)₂NR^(19b)—, —NR^(19b)S(═O)—, or —S(═O)NR^(19b)—;Z is C₁-C₃ alkyl substituted with 1-2 R¹²; aryl substituted with 0-4R^(12b); C₃-C₁₀ carbocycle substituted with 0-4 R^(12b); or 5 to 10membered heterocycle substituted with 0-3 R^(12b); R¹² is C₆-C₁₀ arylsubstituted with 0-4 R^(12b); C₃-C₁₀ carbocycle substituted with 0-4R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃,C₁-C₆ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; B is

R¹¹, at each occurrence, is independently selected from C₁-C₄ alkoxy,Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, C(═O)NR¹⁸R¹⁹, S(═O)₂NR¹⁸R¹⁹,CF₃; C₁-C₆ alkyl substituted with 0-1 R^(11a); aryl substituted with 0-3R^(11b); C₃-C₁₀ carbocycle substituted with 0-3 R^(11b); or 5 to 10membered heterocycle substituted with 0-3 R^(1b); alternatively, two R¹¹substituents on the same or adjacent carbon atoms may be combined toform a C₃-C₆ carbocycle or a benzo fused radical; R^(11a), at eachoccurrence, is independently selected from H, C₁-C₆ alkyl, OR¹⁴, Cl, F,Br, I, ═O, CN, NO₂, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3R^(11b); R^(11b) at each occurrence, is independently selected from H,OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃, C₁-C₆ alkyl, C₁-C₄ alkoxy,C₁-C₄ haloalkyl, and C₁-C₄ haloalkoxy; R¹⁴ is H, phenyl, benzyl, C₁-C₆alkyl, or C₂-C₆ alkoxyalkyl; R¹⁵, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl)and —S(═O)₂—(C₁-C₆ alkyl); R¹⁶, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆alkyl) and —S(═O)₂—(C₁-C₆ alkyl); R¹⁷ is H, aryl, (aryl)CH₂—, C₁-C₆alkyl, or C₂-C₆ alkoxyalkyl; R¹⁸, at each occurrence, is independentlyselected from H, C₁-C₆ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₆ alkyl)and —S(═O)₂—(C₁-C₆ alkyl); and R¹⁹, at each occurrence, is independentlyselected from H, OH, C₁-C₆ alkyl, phenyl, benzyl, phenethyl,—C(═O)-(C₁-C₆ alkyl) and —S(═O)₂—(C₁-C₆ alkyl); and R^(19b) is H, C₁-C₆alkyl, C₃-C₈ cycloalkyl, phenyl, benzyl or phenethyl.
 12. A compound ofclaim 11 of Formula (IIb) wherein:

or pharmaceutically acceptable salt or prodrug thereof, wherein: R³ isR⁴, n is 0 or 1; m is 0 or 1; R⁴ is H, OH, C₁-C₄ alkyl substituted with0-2 R^(4a), C₂-C₄ alkenyl substituted with 0-2 R^(4a), C₂-C₄ alkynylsubstituted with 0-1 R^(4a), C₃-C₆ cycloalkyl substituted with 0-3R^(4b), aryl substituted with 0-3 R^(4b), or 5 to 10 memberedheterocycle substituted with 0-3 R^(4b); R^(4a), at each occurrence, isindependently selected from is H, F, Cl, CF₃, C₃-C₆ cycloalkylsubstituted with 0-3 R^(4b), phenyl substituted with 0-3 R^(4b), or 5 to6 membered heterocycle substituted with 0-3 R^(4b); R^(4b), at eachoccurrence, is independently selected from H, OH, Cl, F, Br, I, CN, NO₂,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R⁵ is H, OR¹⁴; C₁-C₄alkyl substituted with 0-3 R^(5b); C₂-C₄ alkenyl substituted with 0-2R^(5b); or C₂-C₄ alkynyl substituted with 0-2 R^(5b); R^(5b), at eachoccurrence, is independently selected from: H, methyl, ethyl, propyl,butyl, CF₃, OR¹⁴, ═O; C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);phenyl substituted with 0-3 R^(5c); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, Br, I, CN, NO₂, NR¹⁵R¹⁶, CF₃,acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂haloalkyl, and C₁-C₂ haloalkoxy; W is a bond, —CH₂—, —CH(CH₃)—, —CH₂CH₂—or —CH(CH₃)CH₂—; X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, andC₁-C₂ haloalkoxy; Y is a bond, —CH₂—V—, —V—, or —V—CH₂—; V is a bond,—C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Zis C₁-C₂ alkyl substituted with 1-2 R¹²; aryl substituted with 0-4R^(12b); C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to 10membered heterocycle substituted with 0-3 R^(12b); R¹² is arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 10 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, C₁-C₄ alkyl, C₁-C₃alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; B is

R¹¹, at each occurrence, is independently selected from C₁-C₄ alkoxy,Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃; C₁-C₆ alkyl substitutedwith 0-1 R^(11a); phenyl substituted with 0-3 R^(11b); C₃-C₁₀ carbocyclesubstituted with 0-3 R^(11b); or 5 to 10 membered heterocyclesubstituted with 0-3 R^(11b); alternatively, two R¹¹ substituents on thesame or adjacent carbon atoms may be combined to form a cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, or a benzo fused radical; R^(11a),at each occurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴,F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶,CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;R¹⁴ is H, phenyl, benzyl, C₁-C₄ alkyl, or C₂-C₄ alkoxyalkyl; R¹⁵, ateach occurrence, is independently selected from H, C₁-C₄ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄ alkyl); R¹⁶, at eachoccurrence, is independently selected from H, OH, C₁-C₄ alkyl, benzyl,phenethyl, —C(═O)—(C₁-C₄ alkyl) and —S(═O)₂—(C₁-C₄ alkyl); R¹⁷ is H,phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl,4-trifluorophenyl, (4-fluorophenyl)methyl, (4-chlorophenyl)methyl,(4-methylphenyl)methyl, (4-trifluorophenyl)methyl, methyl, ethyl,propyl, butyl, methoxymethyl, methyoxyethyl, ethoxymethyl, orethoxyethyl; R¹⁸ at each occurrence, is independently selected from H,methyl, ethyl, propyl, butyl, phenyl, benzyl, and phenethyl; and R¹⁹, ateach occurrence, is independently selected from H, methyl, and ethyl.13.-23. (canceled)
 24. A pharmaceutical composition comprising acompound of claim 2 or a pharmaceutically acceptable salt thereof, and apharmaceutically acceptable carrier.
 25. A method for the treatment ofAlzheimer's Disease neurological disorders associated with β-amyloidproduction comprising administering to a host in need of such treatmenta therapeutically effective amount of a compound of claim 2 or apharmaceutically acceptable salt thereof.
 26. A method for the treatmentof Alzheimer's Disease associated with β-amyloid production comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of a compound of claim 3 or a pharmaceuticallyacceptable salt thereof.
 27. A method for the treatment of Alzheimer'sDisease associated with β-amyloid production comprising administering toa host in need of such treatment a therapeutically effective amount of acompound of claim 4 or a pharmaceutically acceptable salt thereof.
 28. Amethod for the treatment of Alzheimer's Disease associated withβ-amyloid production comprising administering to a host in need of suchtreatment a therapeutically effective amount of a compound of claim 5 ora pharmaceutically acceptable salt thereof.
 29. A method for thetreatment of Alzheimer's Disease associated with β-amyloid productioncomprising administering to a host in need of such treatment atherapeutically effective amount of a compound of claim 9 or apharmaceutically acceptable salt thereof.
 30. A method for the treatmentof Alzheimer's Disease associated with β-amyloid production comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of a compound of claim 11 or a pharmaceuticallyacceptable salt thereof.
 31. A method for the treatment of neurologicaldisorders associated with β-amyloid production comprising administeringto a host in need of such treatment a therapeutically effective amountof a metalloprotease inhibitor of claim 2 which inhibits γ-secretaseactivity.
 32. The method of claim 31 wherein the metalloproteaseinhibitor is a hydroxamic acid.
 33. The method of claim 31 wherein themetalloprotease inhibitor is a hydroxamic acid with an IC₅₀ value ofless than 10 μM in the Aβ immunoprecipitation assay.
 34. (canceled) 35.A method for the treatment of Alzheimer's Disease comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of a compound of claim 12 or a pharmaceuticallyacceptable salt thereof.
 36. A compound of Formula (Ie),

or a pharmaceutically acceptable salt thereof, wherein: R³ is C₁-C₄alkyl substituted with 0-2 R^(4a), C₂-C₄ alkenyl substituted with 0-2R^(4a), C₂-C₄ alkynyl substituted with 0-2 R^(4a), R^(4a), at eachoccurrence, is independently selected from is H, F, CF₃, C₃-C₆cycloalkyl substituted with 0-3 R^(4b), phenyl substituted with 0-3R^(4b), or 5 to 6 membered heterocycle substituted with 0-3 R^(4b);R^(4b), at each occurrence, is independently selected from H, OH, Cl, F,NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl,butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;R⁵ is C₁-C₄ alkyl substituted with 0-3 R^(5b); C₂-C₄ alkenyl substitutedwith 0-2 R^(5b); or C₂-C₄ alkynyl substituted with 0-2 R^(5b); R^(5b),at each occurrence, is independently selected from: H, methyl, ethyl,propyl, butyl, CF₃, OR¹⁴, ═O; C₃-C₆ cycloalkyl substituted with 0-2R^(5c); phenyl substituted with 0-3 R^(5c); or 5 to 6 memberedheterocycle substituted with 0-2 R^(5c); R^(5c), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; W is a bond, —CH₂— or—CH(CH₃)—; X is a bond; phenyl substituted with 0-2 R^(Xb); C₃-C₆cycloalkyl substituted with 0-2 R^(Xb); or 5 to 6 membered heterocyclesubstituted with 0-2 R^(Xb); R^(Xb), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; Y is a bond, —CH₂—V—,—V—, or —V—CH₂—; V is a bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—,—NH—, —N(CH₃)—, or —N(CH₂CH₃)—, Z is C₁-C₂ alkyl substituted with 1-2R¹²; aryl substituted with 0-4 R^(12b); C₃-C₆ carbocycle substitutedwith 0-3 R^(12b); or 5 to 10 membered heterocycle substituted with 0-3R^(12b); R¹² is aryl substituted with 0-4 R^(12b); C₃-C₆ carbocyclesubstituted with 0-3 R^(12b); or 5 to 10 membered heterocyclesubstituted with 0-3 R^(12b); R^(12b), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃,S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl, propyl, butyl, methoxy, ethoxy,propoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹¹, at each occurrence,is independently selected from C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹,C(═O)R¹⁷, C(═O)OR¹⁷, CF₃; C₁-C₄ alkyl substituted with 0-1 R^(11a);phenyl substituted with 0-3 R^(11b); C₃-C₆ carbocycle substituted with0-3 R^(11b); or 5 to 6 membered heterocycle substituted with 0-3R^(11b); alternatively, two R¹¹ substituents on the same or adjacentcarbon atoms may be combined to form a cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, or a benzo fused radical; R^(11a), at eachoccurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴, F, ═O,NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), at eachoccurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃,C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy; R¹⁴ isH, phenyl, benzyl, methyl, ethyl, propyl, butyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl, andbutyl; and R¹⁶, at each occurrence, is independently selected from H,OH, C₁-C₄ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and—S(═O)₂—(C₁-C₄ alkyl).
 37. A compound of claim 36 of Formula (Ie):

or a pharmaceutically acceptable salt thereof, wherein: R³ is C₁-C₄alkyl substituted with 0-1 R^(4a), C₂-C₄ alkenyl substituted with 0-1R^(4a), C₂-C₄ alkynyl substituted with 0-1 R^(4a), R^(4a) is C₃-C₆cycloalkyl substituted with 0-3 R^(4b), or phenyl substituted with 0-3R^(4b); R^(4b), at each occurrence, is independently selected from H,Cl, F, or methyl; R⁵ is C₁-C₄ alkyl substituted with 0-1 R^(5b); C₂-C₄alkenyl substituted with 0-1 R^(5b); or C₂-C₄ alkynyl substituted with0-1 R^(5b); R^(5b) is H or C₃-C₆ cycloalkyl substituted with 0-2 R^(5c);R^(5c), at each occurrence, is independently selected from H, Cl, F, andmethyl; W is a bond or —CH₂—; X is a bond; phenyl substituted with 0-1R^(Xb); C₃-C₆ cycloalkyl substituted with 0-2 R^(Xb); or pyridylsubstituted with 0-1 R^(Xb); R^(Xb) is H, Cl, F, CF₃, SCH₃, methyl,methoxy, C₁-C₂ haloalkyl, or C₁-C₂ haloalkoxy; Y is a bond or —V—; V isa bond, —C(═O)—, —O—, —S—, —S(═O)—, —S(═O)₂—, —NH—, —N(CH₃)—, or—N(CH₂CH₃)—, Z is C₁-C₂ alkyl substituted with 1-2 R¹²; aryl substitutedwith 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to6 membered heterocycle substituted with 0-3 R^(12b); R¹² is arylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 6 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R¹¹ at each occurrence, is independently selected from C₁-C₄alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃; C₁-C₄ alkylsubstituted with 0-1 R^(11a); phenyl substituted with 0-3 R^(11b); C₃-C₆carbocycle substituted with 0-3 R^(11b); or 5 to 6 membered heterocyclesubstituted with 0-3 R^(11b); alternatively, two R¹¹ substituents on thesame or adjacent carbon atoms may be combined to form a cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, or a benzo fused radical; R^(11a),at each occurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴,F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶,CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;R¹⁴ is H, phenyl, benzyl, methyl, ethyl, propyl, butyl; R¹⁵, at eachoccurrence, is independently selected from H, methyl, ethyl, propyl, andbutyl; and R¹⁶, at each occurrence, is independently selected from H,OH, C₁-C₄ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄ alkyl) and—S(═O)₂—(C₁-C₄ alkyl).
 38. A compound of claim 36 of Formula (Ie)

or a pharmaceutically acceptable salt thereof, wherein: R³ is C₂-C₄alkyl, C₂-C₄ alkenyl, or C₂-C₄ alkynyl; R⁵ is C₁-C₄ alkyl substitutedwith 0-1 R^(5b); R^(5b) is H, cyclopropyl, (methyl)cyclopropyl-,(methyl)cyclobutyl-, cyclobutyl, cyclopentyl, or cyclohexyl; W is a bondor —CH₂—; X is a bond; Y is a bond; Z is methyl substituted with 1-2R¹²; ethyl substituted with 1-2 R¹²; phenyl substituted with 0-4R^(12b); C₃-C₆ carbocycle substituted with 0-3 R^(12b); or 5 to 6membered heterocycle substituted with 0-3 R^(12b); R¹² is phenylsubstituted with 0-4 R^(12b); C₃-C₆ carbocycle substituted with 0-3R^(12b); or 5 to 6 membered heterocycle substituted with 0-3 R^(12b);R^(12b), at each occurrence, is independently selected from H, OH, Cl,F, NR¹⁵R¹⁶, CF₃, acetyl, SCH₃, S(═O)CH₃, S(═O)₂CH₃, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, C₁-C₂ haloalkyl, and C₁-C₂haloalkoxy; R¹¹, at each occurrence, is independently selected fromC₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷, C(═O)OR¹⁷, CF₃; C₁-C₄ alkylsubstituted with 0-1 R^(11a); phenyl substituted with 0-3 R^(11b); C₃-C₆carbocycle substituted with 0-3 R^(11b); or 5 to 6 membered heterocyclesubstituted with 0-3 R^(11b); alternatively, two R¹¹ substituents on thesame or adjacent carbon atoms may be combined to form a cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, or a benzo fused radical; R^(11a),at each occurrence, is independently selected from H, C₁-C₄ alkyl, OR¹⁴,F, ═O, NR¹⁵R¹⁶, CF₃, or phenyl substituted with 0-3 R^(11b); R^(11b), ateach occurrence, is independently selected from H, OH, Cl, F, NR¹⁵R¹⁶,CF₃, C₁-C₄ alkyl, C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy;R¹⁵, at each occurrence, is independently selected from H, methyl,ethyl, propyl, and butyl; and R¹⁶, at each occurrence, is independentlyselected from H, OH, C₁-C₄ alkyl, benzyl, phenethyl, —C(═O)—(C₁-C₄alkyl) and —S(═O)₂—(C₁-C₄ alkyl).
 39. A compound of claim 36 of Formula(Ie)

or a pharmaceutically acceptable salt thereof, wherein: R³ is—CH₂CH₂CH₃, —CH₂CH₂CH₂CH₃, —CH₂(CH₃)₂, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂,—CH₂C(CH₃)₃, —CH═CH₂, —CH₂CH═CH₂, —CH₂C(CH₃)═CH₂, —CH₂CH═C(CH₃)₂,—CH₂CH₂CH═CH₂, —CH₂CH₂C(CH₃)═CH₂, —CH₂CH₂CH═C(CH₃)₂, cis-CH₂CH═CH(CH₃),cis-CH₂CH₂CH═CH(CH₃), trans-CH₂CH═CH(CH₃), trans-CH₂CH₂CH═CH(CH₃),cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—, cyclohexyl-CH₂—,cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—, cyclopentyl-CH₂CH₂—,cyclohexyl-CH₂CH₂—, phenyl-CH₂—, (3,5-diF-phenyl)CH₂—, phenyl-CH₂CH₂—,or (3,5-diF-phenyl)CH₂CH₂—; R⁵ is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₃)₂,—CH₂CH₂CH₂CH₃, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃,—CH₂CH₂CH₂CH₂CH₃, —CH(CH₃)CH₂CH₂CH₃, —CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH(CH₂CH₃)₂, cyclopropyl-CH₂—, cyclobutyl-CH₂—, cyclopentyl-CH₂—,cyclohexyl-CH₂—, (2-CH₃-cyclopropyl)CH₂—, (3-CH₃-cyclobutyl)CH₂—,cyclopropyl-CH₂CH₂—, cyclobutyl-CH₂CH₂—, cyclopentyl-CH₂CH₂—,cyclohexyl-CH₂CH₂—, (2-CH₃-cyclopropyl)CH₂CH₂—, or(3-CH₃-cyclobutyl)CH₂CH₂—; W is a bond or —CH₂—; X is a bond; Y is abond; Z is phenyl, 2-F-phenyl, 3-F-phenyl, 4-F-phenyl, 2-Cl-phenyl,3-Cl-phenyl, 4-Cl-phenyl, 2,3-diF-phenyl, 2,4-diF-phenyl,2,5-diF-phenyl, 2,6-diF-phenyl, 3,4-diF-phenyl, 3,5-diF-phenyl,2,3-diCl-phenyl, 2,4-diCl-phenyl, 2,5-diCl-phenyl, 2,6-diCl-phenyl,3,4-diCl-phenyl, 3,5-diCl-phenyl, 3-F-4-Cl-phenyl, 3-F-5-Cl-phenyl,3-Cl-4-F-phenyl, 2-MeO-phenyl, 3-MeO-phenyl, 4-MeO-phenyl, 2-Me-phenyl,3-Me-phenyl, 4-Me-phenyl, 2-MeS-phenyl, 3-MeS-phenyl, 4-MeS-phenyl,2-CF₃O-phenyl, 3-CF₃O-phenyl, 4-CF₃O-phenyl, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, phenyl-CH₂—, (2-F-phenyl)CH₂—,(3-F-phenyl)CH₂—, (4-F-phenyl)CH₂—, (2-Cl-phenyl)CH₂—,(3-Cl-phenyl)CH₂—, (4-Cl-phenyl)CH₂—, (2,3-diF-phenyl)CH₂—,(2,4-diF-phenyl)CH₂—, (2,5-diF-phenyl)CH₂—, (2,6-diF-phenyl)CH₂—,(3,4-diF-phenyl)CH₂—, (3,5-diF-phenyl)CH₂—, (2,3-diCl-phenyl)CH₂—,(2,4-diCl-phenyl)CH₂—, (2,5-diCl-phenyl)CH₂—, (2,6-diCl-phenyl)CH₂—,(3,4-diCl-phenyl)CH₂—, (3,5-diCl-phenyl)CH₂—, (3-F-4-Cl-phenyl)CH₂—,(3-F-5-Cl-phenyl)CH₂—, (3-Cl-4-F-phenyl)CH₂—, (2-MeO-phenyl)CH₂—,(3-MeO-phenyl)CH₂—, (4-MeO-phenyl)CH₂—, (2-Me-phenyl)CH₂—,(3-Me-phenyl)CH₂—, (4-Me-phenyl)CH₂—, (2-MeS-phenyl)CH₂—,(3-MeS-phenyl)CH₂—, 4-MeS-phenyl)CH₂—, (2-CF₃O-phenyl)CH₂—,(3-CF₃O-phenyl)CH₂—, (4-CF₃O-phenyl)CH₂—, (cyclopropyl)CH₂—,(cyclobutyl)CH₂—, (cyclopentyl)CH₂—, (cyclohexyl)CH₂—, phenyl-CH₂CH₂—,(phenyl)₂CHCH₂—, (2-F-phenyl)CH₂CH₂—, (3-F-phenyl)CH₂CH₂—,(4-F-phenyl)CH₂CH₂—, (2-Cl-phenyl)CH₂CH₂—, (3-Cl-phenyl)CH₂CH₂—,(4-Cl-phenyl)CH₂CH₂—, (2,3-diF-phenyl)CH₂CH₂—, (2,4-diF-phenyl)CH₂CH₂—,(2,5-diF-phenyl)CH₂CH₂—, (2,6-diF-phenyl)CH₂CH₂—,(3,4-diF-phenyl)CH₂CH₂—, (3,5-diF-phenyl)CH₂CH₂—,(2,3-diCl-phenyl)CH₂CH₂—, (2,4-diCl-phenyl)CH₂CH₂—,(2,5-diCl-phenyl)CH₂CH₂—, (2,6-diCl-phenyl)CH₂CH₂—,(3,4-diCl-phenyl)CH₂CH₂—, (3,5-diCl-phenyl)CH₂CH₂—,(3-F-4-Cl-phenyl)CH₂CH₂—, (3-F-5-Cl-phenyl)CH₂CH₂—,(3-Cl-4-F-phenyl)CH₂CH₂—, (2-MeO-phenyl)CH₂CH₂—, (3-MeO-phenyl)CH₂CH₂—,(4-MeO-phenyl)CH₂CH₂—, (2-Me-phenyl)CH₂CH₂—, (3-Me-phenyl)CH₂CH₂—,(4-Me-phenyl)CH₂CH₂—, (2-MeS-phenyl)CH₂CH₂—, (3-MeS-phenyl)CH₂CH₂—,(4-MeS-phenyl)CH₂CH₂—, (2-CF₃O-phenyl)CH₂CH₂—, (3-CF₃O-phenyl)CH₂CH₂—,(4-CF₃O-phenyl)CH₂CH₂—, (cyclopropyl)CH₂CH₂—, (cyclobutyl)CH₂CH₂—,(cyclopentyl)CH₂CH₂—, or (cyclohexyl)CH₂CH₂. R¹¹, at each occurrence, isindependently selected from C₁-C₄ alkoxy, Cl, F, ═O, NR¹⁸R¹⁹, C(═O)R¹⁷,C(═O)OR¹⁷, CF₃; C₁-C₄ alkyl substituted with 0-1 R^(11a); phenylsubstituted with 0-3 R^(11b); C₃-C₆ carbocycle substituted with 0-3R^(11b); or 5 to 6 membered heterocycle substituted with 0-3 R^(11b);alternatively, two R¹¹ substituents on the same or adjacent carbon atomsmay be combined to form a cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, or a benzo fused radical; R^(11a), at each occurrence, isindependently selected from H, C₁-C₄ alkyl, OR¹⁴, F, ═O, NR¹⁵R¹⁶, CF₃,or phenyl substituted with 0-3 R^(11b); R^(11b), at each occurrence, isindependently selected from H, OH, Cl, F, NR¹⁵R¹⁶, CF₃, C₁-C₄ alkyl,C₁-C₃ alkoxy, C₁-C₂ haloalkyl, and C₁-C₂ haloalkoxy.
 40. Apharmaceutical composition comprising a compound of claim 3 or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.
 41. A pharmaceutical composition comprising acompound of claim 4 or a pharmaceutically acceptable salt thereof, and apharmaceutically acceptable carrier.
 42. A pharmaceutical compositioncomprising a compound of claim 5 or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable carrier.
 43. A pharmaceuticalcomposition comprising a compound of claim 9 or a pharmaceuticallyacceptable salt thereof, and a pharmaceutically acceptable carrier. 44.A pharmaceutical composition comprising a compound of claim 11 or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.
 45. A pharmaceutical composition comprising acompound of claim 12 or a pharmaceutically acceptable salt thereof, anda pharmaceutically acceptable carrier.
 46. A pharmaceutical compositioncomprising a compound of claim 36 or a pharmaceutically acceptable saltthereof, and a pharmaceutically acceptable carrier.
 47. A pharmaceuticalcomposition comprising a compound of claim 37 or a pharmaceuticallyacceptable salt thereof, and a pharmaceutically acceptable carrier. 48.A pharmaceutical composition comprising a compound of claim 38 or apharmaceutically acceptable salt thereof, and a pharmaceuticallyacceptable carrier.
 49. A pharmaceutical composition comprising acompound of claim 39 or a pharmaceutically acceptable salt thereof, anda pharmaceutically acceptable carrier.
 50. A method for the treatment ofAlzheimer's Disease comprising administering to a host in need of suchtreatment a therapeutically effective amount of a compound of claim 36or a pharmaceutically acceptable salt thereof.
 51. A method for thetreatment of Alzheimer's Disease comprising administering to a host inneed of such treatment a therapeutically effective amount of a compoundof claim 37 or a pharmaceutically acceptable salt thereof.
 52. A methodfor the treatment of Alzheimer's Disease comprising administering to ahost in need of such treatment a therapeutically effective amount of acompound of claim 38 or a pharmaceutically acceptable salt thereof. 53.A method for the treatment of Alzheimer's Disease comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of a compound of claim 39 or a pharmaceuticallyacceptable salt thereof.